HTR2A、5-HTT基因多态性与云南汉族酒精依赖关联性研究
|
摘要
研究目的
酒精依赖(AD)是一种多因子控制的复杂疾病,而超过一半的饮酒风险度由遗传因素决定。在与酒精依赖相关的神经递质中,5-羟色胺(5-HT)系统受到广泛关注。迄今对5-羟色胺2A受体(HTR2A)和5-羟色胺转运体(5-HTT)基因多态与酒精依赖相关性的研究报道虽多,但结论的矛盾性和差异性仍然存在,并且还未见云南省汉族人群中的相关研究报道。为此,本研究选择云南汉族人群对HTR2A和5-HTT 2个基因7个多态位点进行检测,以探讨其与酒精依赖发生的关系。
研究方法
按照DSM-Ⅳ诊断标准选择2006-2010年五年来云南省精神病医院酒与药物依赖治疗科住院治疗的118例酒精依赖综合征患者作为研究对象,同时选取与上述病例组相匹配的218例健康体检者作为对照。应用PCR-RFLP和PCR测序方法对336个云南汉族HTR2A基因中的rs6311、rs6313、rs6314、rs2296972、rs4941570和rs4941571 6个SNPs和5-HTT基因中的5-HTTLPR共7个位点进行了基因分型,采用SPSS16.0、SHEsis和Arlequin 3.01对结果进行统计和分析。
研究结果
1、单个位点分析结果
在云南汉族人群中,HTR2A基因rs6311(A-1438G)、rs6313(T102C)、rs2296972、rs4941570和rs4941571位点均与酒精依赖无关；5-HTT基因启动子区域5-HTTLPR多态性与酒精依赖存在相关性,酒精依赖患者组和正常对照组的5-HTTLPR的基因型分布存在显著性差异,LL和LS基因的携带者人群嗜酒发生率显著低于SS基因型人群。S和L等位基因频率在两组间无统计学差异,但其分布存在种族差异性。
2、组合基因型分析结果
5-HTTLPR SL/rs6311 AA、SL/rs631377 TT、SL/rs4941571 CC基因型组合使酒精依赖患病风险降低,5-HTTLPR SS/rs6311 GG、SS/rs4941570AA基因型组合使酒精依赖患病风险降升高。结果提示5-HTTLPR与HTR2A基因位点具有协同作用。
2、单倍型分析结果
HTR2A基因的5个SNPs (rs6311、s6313、rs2296972、rs4941570和rs4941571)在云南汉族中构建出11种主要单倍型。总体检验显示HTR2A基因酒精依赖组和正常对照组间的单倍型分布具有显著性差异；H6(GCTGC)单倍型可能使酒精依赖的患病风险升高；H8 (ATGGC)在可能使酒精依赖的患病风险降低。3、连锁不平衡分析
云南汉族人群中,HTR2A基因的rs6311、rs6313、rs4941570及rs4941571之间存在着强连锁(D’>0.8)。
研究结论
在云南汉族人群中,HTR2A基因rs6311(A-1438G)、rs6313(T102C)、rs2296972、rs4941570和rs4941571位点均与酒精依赖无关；5-HTT基因启动子区域5-HTTLPR多态性与酒精依赖存在相关性,LL和LS基因型可能是降低酒精依赖发病的影响因子之一
5-HTTLPR与HTR2A基因存在协同作用。
H6 (GCTGC)单倍型可能使酒精依赖的患病风险升高；H8 (ATGGC)在可能使酒精依赖的患病风险降低。
云南汉族人群中,HTR2A基因的rs6311、rs6313、rs4941570及rs4941571之间存在着强连锁(D’>0.8)。
Objective:Alcohol dependence (AD)is a complex disorder which is influenced by many factors.Studies indicate that hereditary factor plays a dominating role in the process of AD pathogenesis.There have been many research reports regarding the association between HTR2A and 5-HTT gene polymorphisms and AD, but the results are inconsistent and conflicting and never performed in Yunnan Han population. The aim of present study is to study the relation between the six SNPs of human HTR2A and 5-HTT gene polymorphism with alcohol dependence,and to study the etiopathogenesis of AD.
Methods:According to the DSM-IV diagnostic criteria, we selected 118 alcohol dependent patients of Mental Health Center of Yunnan Province and 218 normal people as control group in the period during 2006-2010.A total of 7 variations(six SNPs of the HTR2A gene and 5-HTTLPR of the 5-HTT gene) were genotyped in 336 Yunnan Han individuals using PCR-RFLP and DNA sequencing techniques. The results are made statistical and biological analyzing by using SPSS 16.0、SHEsis and Arlequin 3.01.
Results:
1、The result of single locus analysis
There was no significant association of rs6311(A-1438G)、rs6313(T102C)、rs2296972、rs4941570 and rs4941571 of HTR2A gene between alcohol dependent group and control group in Yunnan Han Population.However,5-HTTLPR polymorphism of the 5-HTT gene might be associated with alcohol dependent patients. Significant differences in genotype frequencies were present between case group and control group of 5-HTTLPR.The proportion of LL and LS genotype was significantly smaller in case group than that was in control group.No significant association was observed in allelic frequencies, which differed in the different ethnic groups.
2、The analysis results of combined haplotypes
When SL of 5-HTTLPR combined with AA of rs6311,or TT of rs6313,or CC of rs4941571,the sick risk would be decreased, When SS of 5-HTTLPR combined with GG of rs6311, or AA of rs4941570,the sick risk would be increased.The results suggested there is a synergistic gene-gene interaction between 5-HTTLPR and HTR2A gene in the pathogenesis of AD.
3、The analysis results of haplotypes for 5 SNPs
The results of haplotype analysis for rs6311、rs6313、rs2296972、rs4941570 and rs4941571 of HTR2A gene revealed that there are 11 kinds of major haplotypes in Yunnan Han Population.The total test showed there were significant differences in the HTR2A gene polymorphisms between alcoholics and controls. H6 (GCTGC) might be a dangerous factor leading to alcohol dependence,H8 (ATGGC) might be significantly associated with increased risks of alcohol dependence.
4、The analysis results of lingkage disequilibrium
Lingkage disequilibrium analysis showed that there were strong linkages between rs631、rs6313、rs4941570 and rs4941571 in Yunnan Han Population. (D' >0.8).
Conclusion:There was no significant association of rs6311(A-1438G) rs6313(T102C)、rs2296972、rs4941570 and rs4941571 of HTR2A gene between AD group and control group in Yunnan Han Population. However,5-HTTLPR polymorphism of 5-HTT gene may be associated with alcohol dependent patients, and the genotype LL or LS may be a genetic factor that responsible for decreasing susceptibility of AD in Yunnan Han population.There is a synergistic gene-gene interaction between 5-HTTLPR and HTR2A gene in the pathogenesis of AD.H6 (GCTGC) might be a dangerous factor leading to AD,H8 (ATGGC) might be significantly associated with increased risks of AD.There were strong linkages between rs6311、rs6313、rs4941570 and rs4941571 in Yunnan Han Population. (D >0.8).
酒精依赖(AD)是一种多因子控制的复杂疾病,而超过一半的饮酒风险度由遗传因素决定。在与酒精依赖相关的神经递质中,5-羟色胺(5-HT)系统受到广泛关注。迄今对5-羟色胺2A受体(HTR2A)和5-羟色胺转运体(5-HTT)基因多态与酒精依赖相关性的研究报道虽多,但结论的矛盾性和差异性仍然存在,并且还未见云南省汉族人群中的相关研究报道。为此,本研究选择云南汉族人群对HTR2A和5-HTT 2个基因7个多态位点进行检测,以探讨其与酒精依赖发生的关系。
研究方法
按照DSM-Ⅳ诊断标准选择2006-2010年五年来云南省精神病医院酒与药物依赖治疗科住院治疗的118例酒精依赖综合征患者作为研究对象,同时选取与上述病例组相匹配的218例健康体检者作为对照。应用PCR-RFLP和PCR测序方法对336个云南汉族HTR2A基因中的rs6311、rs6313、rs6314、rs2296972、rs4941570和rs4941571 6个SNPs和5-HTT基因中的5-HTTLPR共7个位点进行了基因分型,采用SPSS16.0、SHEsis和Arlequin 3.01对结果进行统计和分析。
研究结果
1、单个位点分析结果
在云南汉族人群中,HTR2A基因rs6311(A-1438G)、rs6313(T102C)、rs2296972、rs4941570和rs4941571位点均与酒精依赖无关；5-HTT基因启动子区域5-HTTLPR多态性与酒精依赖存在相关性,酒精依赖患者组和正常对照组的5-HTTLPR的基因型分布存在显著性差异,LL和LS基因的携带者人群嗜酒发生率显著低于SS基因型人群。S和L等位基因频率在两组间无统计学差异,但其分布存在种族差异性。
2、组合基因型分析结果
5-HTTLPR SL/rs6311 AA、SL/rs631377 TT、SL/rs4941571 CC基因型组合使酒精依赖患病风险降低,5-HTTLPR SS/rs6311 GG、SS/rs4941570AA基因型组合使酒精依赖患病风险降升高。结果提示5-HTTLPR与HTR2A基因位点具有协同作用。
2、单倍型分析结果
HTR2A基因的5个SNPs (rs6311、s6313、rs2296972、rs4941570和rs4941571)在云南汉族中构建出11种主要单倍型。总体检验显示HTR2A基因酒精依赖组和正常对照组间的单倍型分布具有显著性差异；H6(GCTGC)单倍型可能使酒精依赖的患病风险升高；H8 (ATGGC)在可能使酒精依赖的患病风险降低。3、连锁不平衡分析
云南汉族人群中,HTR2A基因的rs6311、rs6313、rs4941570及rs4941571之间存在着强连锁(D’>0.8)。
研究结论
在云南汉族人群中,HTR2A基因rs6311(A-1438G)、rs6313(T102C)、rs2296972、rs4941570和rs4941571位点均与酒精依赖无关；5-HTT基因启动子区域5-HTTLPR多态性与酒精依赖存在相关性,LL和LS基因型可能是降低酒精依赖发病的影响因子之一
5-HTTLPR与HTR2A基因存在协同作用。
H6 (GCTGC)单倍型可能使酒精依赖的患病风险升高；H8 (ATGGC)在可能使酒精依赖的患病风险降低。
云南汉族人群中,HTR2A基因的rs6311、rs6313、rs4941570及rs4941571之间存在着强连锁(D’>0.8)。
Objective:Alcohol dependence (AD)is a complex disorder which is influenced by many factors.Studies indicate that hereditary factor plays a dominating role in the process of AD pathogenesis.There have been many research reports regarding the association between HTR2A and 5-HTT gene polymorphisms and AD, but the results are inconsistent and conflicting and never performed in Yunnan Han population. The aim of present study is to study the relation between the six SNPs of human HTR2A and 5-HTT gene polymorphism with alcohol dependence,and to study the etiopathogenesis of AD.
Methods:According to the DSM-IV diagnostic criteria, we selected 118 alcohol dependent patients of Mental Health Center of Yunnan Province and 218 normal people as control group in the period during 2006-2010.A total of 7 variations(six SNPs of the HTR2A gene and 5-HTTLPR of the 5-HTT gene) were genotyped in 336 Yunnan Han individuals using PCR-RFLP and DNA sequencing techniques. The results are made statistical and biological analyzing by using SPSS 16.0、SHEsis and Arlequin 3.01.
Results:
1、The result of single locus analysis
There was no significant association of rs6311(A-1438G)、rs6313(T102C)、rs2296972、rs4941570 and rs4941571 of HTR2A gene between alcohol dependent group and control group in Yunnan Han Population.However,5-HTTLPR polymorphism of the 5-HTT gene might be associated with alcohol dependent patients. Significant differences in genotype frequencies were present between case group and control group of 5-HTTLPR.The proportion of LL and LS genotype was significantly smaller in case group than that was in control group.No significant association was observed in allelic frequencies, which differed in the different ethnic groups.
2、The analysis results of combined haplotypes
When SL of 5-HTTLPR combined with AA of rs6311,or TT of rs6313,or CC of rs4941571,the sick risk would be decreased, When SS of 5-HTTLPR combined with GG of rs6311, or AA of rs4941570,the sick risk would be increased.The results suggested there is a synergistic gene-gene interaction between 5-HTTLPR and HTR2A gene in the pathogenesis of AD.
3、The analysis results of haplotypes for 5 SNPs
The results of haplotype analysis for rs6311、rs6313、rs2296972、rs4941570 and rs4941571 of HTR2A gene revealed that there are 11 kinds of major haplotypes in Yunnan Han Population.The total test showed there were significant differences in the HTR2A gene polymorphisms between alcoholics and controls. H6 (GCTGC) might be a dangerous factor leading to alcohol dependence,H8 (ATGGC) might be significantly associated with increased risks of alcohol dependence.
4、The analysis results of lingkage disequilibrium
Lingkage disequilibrium analysis showed that there were strong linkages between rs631、rs6313、rs4941570 and rs4941571 in Yunnan Han Population. (D' >0.8).
Conclusion:There was no significant association of rs6311(A-1438G) rs6313(T102C)、rs2296972、rs4941570 and rs4941571 of HTR2A gene between AD group and control group in Yunnan Han Population. However,5-HTTLPR polymorphism of 5-HTT gene may be associated with alcohol dependent patients, and the genotype LL or LS may be a genetic factor that responsible for decreasing susceptibility of AD in Yunnan Han population.There is a synergistic gene-gene interaction between 5-HTTLPR and HTR2A gene in the pathogenesis of AD.H6 (GCTGC) might be a dangerous factor leading to AD,H8 (ATGGC) might be significantly associated with increased risks of AD.There were strong linkages between rs6311、rs6313、rs4941570 and rs4941571 in Yunnan Han Population. (D >0.8).
引文
[1]Clarke TK,Treutlein J,Zimmermann US,et al.HPA-axis activity in alcoholism:examples for agene-environment interaction[J]Addict Biol,2008,13(1);1-14.
[2]Tyndale RF.Genetics of alcohol and tobacco use in humans[J].Ann Med,2003,35 (2),94-121.
[3]石葛明,李双成,崔慧先等.5-羟色胺转运体在酗酒人脑干头侧中缝核群的表达[J].解剖学杂志,2006,29(2)：213-215.
[4]李双成,石雄,石葛明等.酗酒与扣带回前部膝周皮质5-羟色胺转运体的表达[J].临床荟萃,2005,20(20)：1153-1155.
[5]Storvik M, Tiihonen J, Haukijarvi T,et al.Amygdala serotonin transporters in alcoholics measured by whole hemisphere autoradiography[J].Synapse,2007 61(8):629-636. [6] Storvik M, Haukijarvi T, Tupala E,et al.Correlation between the SERT binding densities in hypothalamus and amygdala in Cloninger type 1 and 2 alcoholics[J].Alcohol,2005,43(1):25-30.
[7]Underwood MD, Mann JJ, Huang YY, et al. Family history of alcoholism is associated with lower 5-HT2A receptor binding in the prefrontal cortex[J].Alcohol Clin Exp Res,2008, 32:593-599.
[8]Agarwal DP.Molecular genetic aspects of alcohol metabolism and alcoholism[J]. Pharmaco psychiatry,1997,30(3):79-84.
[9]Chen WJ,Loh E-W,Hsu Y-PP,et al.Alcohol-metabolising genes and alcoholism among Taiwanese Hanmen:independent effect of ADH2,ADH3, and ALDH2[J].Br J Psychiatry, 1996b,168(6):762-767.
[10]Maezawa Y,Yamauchi M,Suzuki TG,et al.Alcohol-metabolizing enzyme polymerphisms and alcoholism in Japan[J].Alcohol Clin Exp Res,1995,19(4):951-954.
[ll]Muramatsu T,Wang ZC,Fang YR, et al.Alcohol and aldehyde dehydrogenase genotypes and drinking behavior of Chinese living in Shanghai[J].Hum Genet,1995,96(2):151-154.
[12]Nakamura K,Iwahashi K,Matsuo Y,et al.Characteristics of Japanese alcoholics with the atypical aldehyde dehydrogenase 2*2.I. A comparison of the genotypes of ALDH2VADH2, ADH3, and cytochrome P-4502E1 between alcoholics and nonalcoholics[J].Alcohol Clin Exp Res,1996, 20(1):52-55.
[13]Shen YC,Fan JH,Edenberg HJ,et al.Polymorphism of ADH and ALDH genes among four ethnic groups in China and effects upon the risk for alcoholism[J]. Alcohol Clin Exp Res,1997, 21(7):1272-1277.
[14]Lee HC,Lee HS,Jung S-H,et al.Association between polymorphisms of ethanol-metabolizing enzymes and susceptibility to alcoholic cirrhosis in a Korean male population[J].J Korean Med Sci,2001,16(6):745-750.
[15]Yasunami M,Kikuchi I,Sarapata D,et al.The human class Ⅰ alcohol dehydrogenase gene cluster:three genes are tandemly organized in an 80-kb-long segment of the genome[J].Genomics, 1990,7(2):152-158.
[16]贺艮峰.酒精依赖综合征与ADH2、CYP4502E1基因多态性的相关研究.云南昆明：昆明医学院,2008
[17]高丽波,钟树荣,景强等.云南汉族酒精依赖综合征与ADH2、ALDH2基因多态性的关联研究[J],医学研究杂志,2010,39(3)：35-39.
[18]Lucki I.The spectrum of behaviors influenced by serotonin.Biol Psychiatry,1998,44:151-162.
[19]Veenstra-VanderWeele J,Anderson GM,Cook EH Jr.Pharmacogenetics and the serotonin systemrinitial studies and future directions[J].Eur J Pharmacol,2000,410:165-181.
[20]Gingrich JA, Ansorge MS,Merker R,et al.New lessons from knockout mice:The role of serotonin during development and its possible contribution to the origins of neuropsychiatric disorders[J].CNS Spectr.2003;8:572-7.
[21]Fisher PM,Munoz KE,Hariri AR.Identification of neurogenetic pathways of risk for psychopathology[J]. Am J Med Genet C Semin Med Genet,,2008,2:147'-153.
[22]D'Souza UM,Craig IW.Functional polymorphisms in dopamine and serotonin pathway genes[J].Hum Mutat,2006,1:1-13.
[23]Norton N and Owen MJ.HTR2A:Association and expression studies in neuropsychiatric Genelics[J] Annals of Medicine,2005,31:121-129.
[24]Pandy SC,Piano M,Schwertz DW,et al.Effect of ethanol dependence and withdrawal on serotonin 2 receptors and phosphoinositide system in rat brain[J]Alcohol Clin Exp Res,1992,16: 392-396.
[25]LeMarquand D, Pihl RO, Benkelfat C.Serotonin and alcohol intake, abuse, and dependence: findings of animal studies[J].Biol Psychiatry,1994,36(6):395-421.
[26]LeMarquand D, Pihl RO, Benkelfat C.Serotonin and alcohol intake, abuse, and dependence: clinical evidence[J].Biol Psychiatry,1994,36(5):326-337.
[27]Lesch KP.Alcohol dependence and gene x environment interaction in emotion regulation:Is serotonin the link[J]? Eur J Pharmacol,2005,1:113-124.
[28]Vengeliene V,BilbaoA,Molander A,et al.Neuropharmacology of alcohol addiction[J].Br J Pharmacol,2008,2:299-315.
[29]Bowirrat A and Oscar-Berman M. Relationship between dopaminergic neurotransmission, alcoholism, and Reward Deficiency syndrome[J]. Am J Med Genet B Neuropsychiatr Genet. 2005,132B(1):29-37.
[30]Bunney EB,Appel SB,Brodie MS.Cocaine potentiates ethanol-induced excitation of dopaminergic reward neurons in the ventral tegmental area[J].J Pharmacol Exp Ther, 2000,293(2):383-390.
[31]Nocjarc C,Roth BL,Pehek A.Localization of 5-HT2Areceptors on dopamine cells in subnuclei of the midbrain A10 cell group[J].Neurosci,2002,111(1):163-178.
[32]Marques FZ, Hutz MH, Bau CH. Influence of the serotonin transporter gene on comorbid disorders among alcohol-dependent individuals[J].Psychiatr Gene,2006,16(3):125-131
[33]Gorwood P, Batel P, Ades J, Hamon M, Boni C.Serotonin transporter gene polymorphisms, alcoholism, and suicidal behavior[J].Biol Psychiatry,2000,48(4):259-264.
[34]Sellers EM, Higgins GA, Sobell MB.5-HT and alcohol abuse[J].TIPS,1992,13:69-75.
[35]Higuchi S, Suzuki K, Yamada K,et al.Alcoholics with eating disorders:prevalence and clinical course:a study fromJapan[J].Br J Psychiatry,1993,162:403-406.
[36]Chen K,Yang W,Grimsby J,et al.The human 5HT2A receptor is encoded by a multiple intron-exon gene[J].Brain Res Mol Brain Res,1992,14:20-26.
[37]Parsons MJ,D'Souza UM, Arranz MJ,et al.The-1438A/G polymorphism in the 5-hydroxytryptamine type 2A receptor gene affects promoter activity[J].Biol Psychiatry,2004,56: 406-410.
[38]Spurlock G,Heils A,Holmans P,et al.A family based association study of T102C polymorphism in 5HT2A and schizophrenia plus identification of new polymorphisms in the promoter[J]. Mol Psychiatry,1998,3:42-49.
[39]Kouzmenko AP,Scaffidi A,Pereira AM,et al.No correlation between A(-1438)G polymorphism in 5-HT2A receptor gene promoter and the density of frontal cortical 5-HT2A receptors in schizophrenia[J].Hum Hered,1999,49:103-105.
[40]Arranz MJ,Munro J,Birkett J,et al.Pharmacogenetic prediction of clozapine response[J]. Lancet,2000,355:1615-1616.
[41]Kusumi I,Suzuki K,Sasaki Y,et al.Serotonin5-HT(2A) receptor gene polymorphism,5-HT(2A) receptor function and personality traits in healthy subjects:A negative study[J].JAffect Disord, 2002,68:235-241.
[42]Bray NJ,Buckland PR,Hall H,et al.The serotonin-2A receptor gene locus does not contain common polymorphism affecting mRNA levels in adult brain[J].Mol Psychiatry,2004,9:109-114.
[43]Mata I,Arranz MJ,Patino A,et al.Serotonergic polymorphisms and psychotic disorders in populations from North Spain[J].Am J Med Genet B Neuropsychiatr Genet,2004,126:88-94.
[44]Martinez-Barrondo S,Saiz PA,Morales B,et al.Serotonin gene polymorphisms in patients with panic disorder[J].Actas Esp Psiquiatr,2005,33:210-216.
[45]Saiz PA,Garcia-Portilla MP,Arango C,et al.Association study of serotonin 2Areceptor (5-HT2A) and serotonin transporter(5-HTT) gene polymorphisms with schizophrenia[J].Prog Neuropsychopharmacol Biol Psychiatry,2001,31:741-745.
[46]Nielsen K,Brask D,Knudsen GM, et al.Immunodetection of the serotonin transporter protein is a more valid marker for serotonergic fibers than serotonin[J].Synapse,2006,59(5):270-276
[47]Lesch KP,Balling U,Gross J,et al.Organization of the human serotonin transporter gene[J].J Neural Transm Gen Sect,1994,95(2):157-162.
[48]Hranilovic D,Stefulj J,Schwab S,et al.Serotonin transporter promoter and intron 2 polymorphisms:relationship between allelic variants and gene expression[J].Biol Psychiatry, 2004,55(11):1090-1094.
[49]Heils A,Teufel A,Petri S,et al.Allelic variation of human serotonin transporter gene expression[J].J Neurochem,1996,66(6):2621-2624.
[50]Greenberg BD,Tolliver T J,Huang S J,et al.Genetic variation in the serotonin transporter promoter region affects serotonin uptake in human blood platelets[J]. Am J Med Genet,1999, 88(1):83-87.
[51]Reimold M, Smolka MN, Schumann G,et al.Midbrain serotonin transporter binding potential measured with [11C]DASB is affected by serotonin transporter genotype[J]. J Neural Transm, 2007,114(5):635-639.
[52]Bradley SL,Dodelzon K,Sandhu HK,et al.Relationship of serotonin transporter gene polymorphisms and haplotypes to mRNA transcription[J].Am J Med Genet B Neuropsychiatr Genet,2005,136B(1):58-61.
[53]Philibert RA,Sandhu H,Hollenbeck N,et al.The relationship of 5HTT (SLC6A4) methylation and genotype on mRNA expression and liability to major depression and alcohol dependence in subjects from the Iowa Adoption Studies[J].Am J Med Genet B Neuropsychiatr Genet,2008, 147B(5):543-549.
[54]吴艳茹,肖泽萍,禹顺英,范娟,汪栋祥.5-羟色胺转运体启动子基因多态与青少年抑郁症患者人格特质的关联研究[J].中国神经精神疾病杂志,2009,35(4)：234-237.
[55]Gokturk C,Schultze S,Nilsson KW,et al.Serotonin transporter (5-HTTLPR) and monoamine oxidase (MAOA) promoter polymorphisms in women with severe alcoholism[J].Arch Womens Ment Health,2008,11(5-6):341-355.
[56]Thompson MD,Gonzalez N,Nguyen T,et al. Serotonin transporter gene polymorphisms in alcohol dependence[J].Alchohol,2000,22(2):61-67.
[57]Konishi T,Luo HR,Calvillo M,et al.ADH1B*1, ADH1C*2, DRD2 (-141C Ins), and 5-HTTLPR are associated with alcoholism in Mexican American men living in Los Angeles[J]. Alcohol Clin Exp Res,2004,28(8):1145-1152.
[58]K6hnke MD,Kolb W,Lutz U,et al.The serotonin transporter promotor polymorphism 5-HTTLPR is not associated with alcoholism or severe forms of alcohol withdrawal in a German sample[J].Psychiatr Genet,2006,16(6):227-228.
[59]Gorwood P, Lanfumey L, Hamon M. Alcohol dependence and polymorphisms of serotonin-related genes[J].Med Sci (Paris),2004,20(12):1132-1138.
[60]Hallikainen T,Saito T,Lachman HM,et al.Association between low activity serotonin transporter promoter genotype and early onset alcoholism with habitual impulsive violent behavior[J].Mol Psychiatry,1999,4(4):385-388.
[61]Matsushita S,Yoshino A,Murayama M,et al.Association study of serotonin transporter gene regulatory region polymorphism and alcoholism[J]. Am J Med Genet,2001 Jul 8;105(5):446-450.
[62]Lee YS, Choi SW, Han DH,et al.Clinical manifestation of alcohol withdrawal symptoms related to genetic polymorphisms of two serotonin receptors and serotonin transporter[J].Eur Addict Res,2009,15(1):39-46.
[63]严卫丽.复杂疾病全基因组关联研究进展—遗传统计分析[J].遗传2008(05)：543-549.
[64]Myers RL,Airey DC,Manier DH,et al.Polymorphisms in the regulatory region of the human serotonin 5-HT2A receptor gene (HTR2A) influence gene expression[J].Bio Psychiatry,2007, 61:167-173.
[65]Nakamura T,Matsushita S,Nishiguchi N,et al.Association of a polymorphismof the 5HT2A receptor gene promoter region with alcohol dependence[J].Mol Psychiatry,1999,4:85-88.
[66]Parsian A,Cloninger CR.Serotonergic pathway genes and subtypes of alcoholism:association studies[J].Psychiatr Genet,2001,11(2):89-94.
[67]Cloninger CR.Neurogenetic adaptive mechanisms in alcoholism.Science,1987,236:410-416.
[68]Aubert R,Betoulle D,Herbeth B,et al.5-HT2A receptor gene polymorphism is associated with food and alcohol intake in obese people[J].Int J Obes Relat Metab Disord,2000,24 (7):920-924.
[69]Polina ER,Contini V,Hutz MH,et al.The serotonin 2A receptor gene in alcohol dependence and tobacco smoking[J].Drug Alcohol Depend,2009,101,128-131.
[70]Preuss UW,Koller G,Bondy B, et al.Impulsive traits and 5-HT2A receptor promoter polymorphism in alcohol dependents:possible association but no influence of personality disoTdeis[J].Neuro psychobiology,2001,43,186-191.
[71]曹莉萍,李涛,许珂等.海洛因依赖与5-HT2A受体基因-1438A/G多态性的相关研究[J].中国药物依赖性杂志,2002,11(4)：266-268
[72]邵春红,江开达,李一峰.5-羟色胺2A受体基因多态与海洛因成瘾渴求程度的关联分析[J].中国神经精神疾病杂志,2005,31(5):321-325.
[73]张英,刘盈.5-HTR2A基因-1438A/G多态性与重性抑郁障碍药效学作用的关联研究[J].辽宁沈阳：中国医科大学,2008.
[74]喻妍,赵靖平,吴仁容等.5-羟色胺2A受体基因-1438A/G多态性与抑郁症的关联研究[J].国际精神病学杂志,2009,36(2)：65-68.
[75]Guhathakurta S,Singh AS,Sinha S,et al.Analysis of serotonin receptor 2Agene (HTR2A): Association study with autism spectrum disorder in the Indian population and investigation of the gene expression in peripheral blood leukocytes[J]. Neurochem Int,2009,55:754-759
[76]Zoroglu SS,Erdal ME,Erdal N,et al.No evidence for an association between the T102C and 1438G/A polymorphisms of the serotonin 2A receptor gene in attention deficit/hyperactivity disorder in a Turkish population[J].Biol Psychiatry,2003,47:17-20.
[77]Enoch MA,Kaye WH,Rotondo A,et al.5-HT2A promoter polymorphism-1438 G/A, anorexia nervosa,and obsessive-compulsive disorder[J].Lancet,1998,351:1785-1786.
[786]Hinney A,Remschmidt H,Hebebrand J.Candidate gene polymorphisms in eating disorders[J]. Eur J Pharmacol,2000,410:147-159.
[79]Saiz PA,Garcia-Portilla MP, Arango C,et al.2008. Association study between obsessive-compulsive disorder and serotonergic candidate genes[J].Prog Neuropsychopharmacol Biol Psychiatry,32:165-770.
[80]Sorli JV, Frances F,Gonzolez JI,et al.Impact of the-1438G>A polymorphism in the serotonin 2A receptor gene on anthropometric profile and obesity risk:a case-control study in a Spanish Mediterranean population[J].Appetite,2008,50:260-265.
[81]Saiz PA,Garcia-Portilla MP, Florez G,et al. Differential role of serotonergic polymorphisms in alcohol and heroin dependence[J].Prog Neuropsychopharmacol Biol Psychiatry,2009,33:695-700.
[82]Turecki G,Briere R,Dewar K,et al.Prediction of level of serotonin 2A receptor binding by serotonin receptor 2A genetic variation in postmortem brain samples from subjectswho did or did not commit suicide[J].Am J Psychiatry,1999,156:1456-1458.
[83]Khait VD,Huang YY,Zalsman G,et al.Association of serotonin 5-HT2A receptor binding and the T102C polymorphism in depressed and healthy Caucasian subjects[J].NeuroPsychoPharmaco-logy,2005,30:166-112.
[84]Polesskaya OO,Sokolov BP.Differential expression of the "C" and "T"alleles of the 5-HT2A receptor gene in the temporal cortex of normal individuals and schizophrenics[J].J Neurosici Res 2002,67:812-822.
[85]Lane HY,Chang YC,Chiu CC et al. Association of risperidone treatment response with a polymorphism in the 5-HT(2A) receptor gene[J].Am J Psychiatry,2002,159:1593-1595.
[86]Du L,Faludi G,Palkovits M, et al.Frequency of long allele in serotonin transporter gene is increased in depressed suicide victims[J].Biol Psychiatry,1999,46:196-201.
[87]Kouzmenko AP,Hayes WL,Pereira AM,et al.5-HT2A receptor polymorphism and steady state receptor expression in schizophrenia[J].Lancet,1997,349:1815-1820.
[88]Kouzmenko AP,Scaffidi A,Pereira AM,et al.No correlation between A(-1438)G polymorphism in 5-HT2A receptor gene promoter and the density of frontal cortical 5-HT2A receptors in schizophrenia[J].Hum Hered,1999,49:103-105.
[89]Bray NJ,Buckland PR,Hall H,et al.The serotonin-2A receptor gene locus does not contain common polymorphism affecting mRNA levels in adult brain.Mol Psychiatry,2004,9:109-114
[90]Hwu HG,Chen CH,Association of 5-HT2A receptor gene polymorphism and alcohol abuse with behavior problems[J].AmJ Med Genet,2000,96(6):797-800.
[91]仲爱芳,汪广剑,张理义.酒精依赖与5-HT2A受体基T102C多态性的相关研究[J].中华实用医学,2003,5(15)：32-33.
[92]Hill EM,Stoltenberg SF,Bullard KH,et al. Antisocial alcoholism and serotonin-related polymorphisms:association tests[J].Psychiatric Genetics,2002,12(3):143-153.
[93]Himei A,Kono Y,Yoneda H,et al. An association study between alcoholism and the serotonergic receptor genes[J]. Alcohol Clin Exp Res,2000,24:341-342.
[94]Yoshihara E,Nakamura K,Itoh M,et al.2000.The human serotonin receptor gene (HTR2) Mspl polymorphism in Japanese schizophrenic and alcoholic patients[J].Neuropsychobiology,41:124-126.
[95]Schuckit MA,Mazzanti C,Smith TL,et al. Selective Genotyping for the Role of 5-HT2A, 5-HT2C and GABAa6 Receptors and the Serotonin Transporter in the Level of Response to Alcohol:A Pilot Study[J].Biol Psychiary,1999;45:647-651
[96]Fehr C,Schleicher A,Szegedi A,et al.Serotonergic polymorphisms in patients suffering from alcoholism, anxiety disorders and narcolepsy[J].Prog Neuropsychopharmacol Biol Psychiatry, 2001,25:965-982.
[97]Wojnar M,Brower KJ,Strobbe S,et al.A Association Between Val66Met Brain-Derived Neurotrophic Factor (BDNF) Gene Polymorphism and Post-Treatment Relapse in Alcohol Dependence[J].Alcohol Clin Exp Res,2009,33(4):693-702.
[98]Drago A,Liappas I,Petio C,et al. Epistasis between ILIA, IL1B, TNF, HTR2A,5-HTTLPR and TPH2 Variations Does Not Impact Alcohol Dependence Disorder Features[J].Int J Environ Res Public Health,2009,6,1980-1990.
[99]Choi JH, Zhang SY, Park KW,et al.The Association between the T102C Polymorphism of the HTR2A Serotonin Receptor Gene and HDL Cholesterol Level in Koreans[J].J Biochem Mol Biol, 2005,38, (2):238-242
[100]Bondy B,Kuznik Jbaghai T,et al.Lack of association of serotonin-2A receptor gene polymorphism (T102C) with suicidal ideation and suicide[J].Am. JMed Genet,2000,96,831-835.
[101]Yu BN,Wang A,Zhou G,et al.T102C genetic polymorphism of the 5-HT2A receptor in Chinese hypertensive patients and healthy controls[J].Clin Exp Pharmacol Physiol,2004,31, 847-849.
[102]Ozaki N, Manji H, Lubierman V,et al. A naturally occurring amino acid substitution of the human serotonin 5-HT2A receptor influences amplitude and timing of intracellular calcium mobilization[J].J Neurochem,1997,68(5):2186-93.
[103]Hazelwood LA, Sanders-Bush E. His452Tyr polymorphism in the human 5-HT2A receptor destabilizes the signaling conformation[J].Mol Pharmacol,2004,66(5):1293-1300.
[104]Yasseen B,Kennedy JL, Zawertailo LA et al.Comorbidity between bipolar disorder and alcohol use disorder:Association of dopamine and serotonin gene polymorphisms[J].Psychiatry Res,2010,176:30-33.
[105]Guhathakurta S,Singh AS,Sinha S,et al.Analysis of serotonin receptor 2A gene (HTR2A): Association study with autism spectrum disorder in the Indian population and investigation of the gene expression in peripheral blood leukocytes[J].Neurochem Int,2009,55:754-759.
[106]Ni X,Bismil R,Chan K,et al. Serotonin 2A receptor gene is associated with personality traits, but not to disorder, in patients with borderline personality disorder[J]. Neurosci Lett,2006,408: 214-219.
[107]Wilkie MJ,Smith G,Day RK,et al.2008. Polymorphisms in the SLC6A4 and HTR2A genes influence treatment outcome following antidepressant therapy[J].Pharmaco genomics J,2009,9: 61-70
[108]Kan JL,Green MR.Pre-mRNA splicing of IgM exons M1 and M2 is directed by a juxtaposed splicing enhancer and inhibitor[J].Genes Dev,1999,13(4):462-471.
[109]Brockmoller J,Cascorbi I,Kerb R,et al.Polymorphisms in xenobiotic conjugation and disease predisposition[J].Toxicol Lett,1998,102-103:173-183.
[110]Excoffier L,Slatkin M.Maximum-likelihood estimation of molecular haplotype frequencies in a diploid population[J]. Mol Biol Evol,1995,12(5):921-927.
[111]Rioux JD,Daly MJ,Silverberg MS,et al.Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease[J].Nat Genet,2001,29:223-228.
[112]高树贵,刘少文,蔡贵庆等.5-羟色胺转运体基因启动子区与心境障碍的关联分析[J].上海精神医学,2004,16(3)：141-144.
[113]唐牟尼,李涛,刘协和等.载脂蛋白E、5-羟色胺转运体基因多态性与阿尔茨海默病的关联分析[J].中华精神科杂志,2000,33(3)：145-148.
[114]Hammoumi S, Payen A, Favre JD, Balmes JL, Benard JY, Husson M, Ferrand JP, Martin JP, Daoust M.Does the short variant of the serotonin transporter linked polymorphic region constitute a marker of alcohol dependence[J]? Alcohol,1999,17(2):107-112.
[115]Lichtermann D, Hranilovic D, Trixler M, Franke P, Jernej B, Delmo CD, Knapp M, Schwab SG, Maier W, Wildenauer DB. Support for allelic association of a polymorphic site in the promoter region of the serotonin transporter gene with risk for alcohol dependence[J].Am J Psychiatry,2000, 157(12):2045-2047.
[116]Kranzler H, Lappalainen J, Nellissery M, Gelernter J. Association study of alcoholism subtypes with a functional promoter polymorphism in the serotonin transporter protein gene[J]. Alcohol Clin Exp Res,2002,26(9):1330-1335.
[117]Foley PF, Loh EW, Innes DJ, Williams SM, Tannenberg AE, Harper CG, Dodd PR.Association studies of neurotransmitter gene polymorphisms in alcoholic Caucasians[J].Ann N YAcad Sci,2004,1025:39-46.
[118]Feinn R, Nellissery M, Kranzler HR. Meta-analysis of the association of a functional serotonin transporter promoter polymorphism with alcohol dependence[J].Am J Med Genet B Neuropsychiatr Genet,2005,133B(1):79-84.
[119]McHugh RK, Hofmann SG, Asnaani A, Sawyer AT, Otto MW. The serotonin transporter gene and risk for alcohol dependence:a meta-analytic review[J]. Drug AlcoholDepend,2010,108(1-2): 1-6.
[120]Saiz PA, Garcia-Portilla MP, Arango C, et al. Association between heroin dependence and 5-HT2A recep tor gene polymorphisms[J].Eur Addict Res,2008,14 (1):47-52.
[121]李恒芬.5-HT信号传导相关SNPs与心境障碍.云南昆明：中南大学,2008.
[122]武颖.5-HT传导通路相关基因多态性与重性抑郁症的关联性研究.山西太原：山西医科大学,2008.
[1]Tsuang MT,Bar JL,Harley RM,et al.The Harvard Twin Study of Substance Abuse:what we have learned[J].Harv Rev Psychiatry,2001,9:267-279.
[2]Shih RA,Belmonte PL,Zandi PP.A review of the evidence from family, twin and adoption studies for a genetic contribution to adult psychiatric disorders[J].Int Rev Psychiatry,2004,16 (4):260-283.
[3]Uhl GR, Drgon T, Johnson C,et al.Higher order addiction molecular genetics:Convergent data from genome-wide association in humans and mice[J].Biochem Pharmacol,2008,75:98-111.
[4]Filip M, Frankowska M, Zaniewska M,et al.The serotonergic system and its role in cocaine addiction[J].Pharmacol Rep,2005,57:685-700.
[5]Higgins GA,Fletcher PJ.Serotonin and drug reward:focus on 5-HT 2C receptors[J].Eur J Pharmacol,2003,480:151-162.
[6]Johnson BA:Role of the serotonergic system in the neurobiology of alcoholism:implications for treatment[J].CNS Drugs,2004,18:1105-1118.
[7]Lucki I.The spectrum of behaviors influenced by serotonin[J].Biol Psychiatry,1998,44: 151-162.
[8]Veenstra-VanderWeele J,Anderson GM,Cook EH Jr.Pharmacogenetics and the serotonin system:initial studies and future directions[J].Eur J Pharmacol,2000,410:165-181.
[9]Gingrich JA, Ansorge MS,Merker R,et al.New lessons from knockout mice:The role of serotonin during development and its possible contribution to the origins of neuropsychiatric disorders[J].CNS Spectr.2003;8:572-7.
[10]Sills TL,Fletcker PJ.Fluoxetine attenuates morphine-induced locomotion and blocks morphine-sensitization[J].Eur J Pharmacol,1997,337:161-164.
[11]Parsons LH,Koob GF,Weiss F.Serotonin dysfunction in the nucleus accumbens of rats during withdrawal after unlimited access to intravenous cocaine[J].J Pharmacol ExpTher,1995,274:1182-1187.
[12]Little KY,Patel UN,Clark TB,et al.Alteration of brain dopamine and serotonin levels in cocaine users:a prekuminary report [J]. Am J Psychiatry,1996,153(9):1216-1218.
[13]Bowirrat A and Oscar-Berman M. Relationship between dopaminergic neurotransmission, alcoholism, and Reward Deficiency syndrome[J]. Am J Med Genet B Neuropsychiatr Gene,. 2005,132B(1):29-37.
[14]DackisC,Brien C.Neurobiology of addiction:treatment and public policy ramifications[J]. Nat Neurosci,2005,8:1431-1436.
[15]王学铭.精神与精神病的生物化学[M].北京：人民卫生出版社,2002,268-269
[16]Chen K,Yang W,Grimsby J,et al.The human 5HT2A receptor is encoded by a multiple intron-exon gene[J].Brain Res Mol Brain Res,1992,14:20-26.
[17]Parsons MJ,D'Souza UM, Arranz MJ,et al.The-1438A/G polymorphism in the 5-hydroxy- tryptamine type 2A receptor gene affects promoter activity[J].Biol Psychiatry,2004,56:406-410.
[18]Nakamura T,Matsushita S,Nishiguchi N,et al.Association of a polymorphismof the 5HT2A receptor gene promoter region with alcohol dependence[J].Mol Psychiatry,1999,4:85-88.
[19]曹莉萍,李涛,许珂等.海洛因依赖与5-HT2A受体基因-1438A/G多态性的相关研究[J].中国药物依赖性杂志,2002,11(4):266-268
[20]邵春红,江开达,李一峰.5-羟色胺2A受体基因多态与海洛因成瘾渴求程度的关联分析[J].中国神经精神疾病杂志,2005,31(5):321-325.
[21]张英,刘盈.5-HTR2A基因-1438A/G多态性与重性抑郁障碍药效学作用的关联研究[J].辽宁沈阳：中国医科大学,2008.
[22]喻妍,赵靖平,吴仁容等.5-羟色胺2A受体基因-1438A/G多态性与抑郁症的关联研究[J].国际精神病学杂志,2009,36(2):65-68.
[23]Guhathakurta S,Singh AS,Sinha S,et al.Analysis of serotonin receptor 2A gene (HTR2A): Association study with autism spectrum disorder in the Indian population and investigation of the gene expression in peripheral blood leukocytes[J]. Neurochem Int,2009,55(8):754-759
[24]Zoroglu SS,Erdal ME,Erdal N,et al.No evidence for an association between the T102C and 1438G/A polymorphisms of the serotonin 2A receptor gene in attention deficit/hyperactivity disorder in a Turkish population[J].Biol Psychiatry,2003,47:17-20.
[25]Enoch MA,Kaye WH,Rotondo A,et al.5-HT2A promoter polymorphism-1438 G/A, anorexia nervosa,and obsessive-compulsive disorder[J].Lancet,1998,351 (9118):1785-1786.
[26]Hinney A,Remschmidt H,Hebebrand J.Candidate gene polymorphisms in eating disorders[J]. Eur J Pharmacol,2000,410:147-159.
[27]Saiz PA,Garcia-Portilla MP, Arango C,et al.2008. Association study between obsessive-compulsive disorder and serotonergic candidate genes[J]. Prog Neuropsychopharmacol Biol Psychiatry,32:765-770.
[28]Sorli JV, Frances F,Gonzalez JI,et al.Impact of the-1438G>A polymorphism in the serotonin 2A receptor gene on anthropometric profile and obesity risk:a case-control study in a Spanish Mediterranean population[J].Appetite,2008,50:260-265.
[29]Choi JH, Zhang SY, Park KW,et al.The Association between the T102C Polymorphism of the HTR2A Serotonin Receptor Gene and HDL Cholesterol Level in Koreans[J]. J Biochem Mol Biol, 2005,38(2):238-242
[30]Bondy B,Kuznik Jbaghai T,et al.Lack of association of serotonin-2A receptor gene polymorphism (T102C) with suicidal ideation and suicide[J].Am J Med Genet,2000,96,831-835.
[31]Yu BN,Wang A,Zhou G,et al.T102C genetic polymorphism of the 5-HT2A receptor in Chinese hypertensive patients and healthy controls[J].Clin Exp Pharmacol Physiol,2004,31,847-849.
[32]Fehr C,Schleicher A,Szegedi A,et al.Serotonergic polymorphisms in patients suffering from alcoholism, anxiety disorders and narcolepsy[J].Prog Neuropsychopharmacol Biol Psychiatry, 2001,25:965-982.
[33]Wojnar M,Brower KJ,Strobbe S,et al.A Association Between Va166Met Brain-Derived Neurotrophic Factor (BDNF) Gene Polymorphism and Post-Treatment Relapse in Alcohol Dependence[J].Alcohol Clin ExpRes,2009,33(4):693-702.
[34]Guhathakurta S,Singh AS,Sinha S,et al.Analysis of serotonin receptor 2A gene (HTR2A): Association study with autism spectrum disorder in the Indian population and investigation of the gene expression in peripheral blood leukocytes[J].Neurochem Int,2009,55:754-759.
[35]Ni X,Bismil R,Chan K,et al.Serotonin 2A receptor gene is associated with personality traits, but not to disorder, in patients with borderline personality disorder[J].Neurosci Lett,2006, 408(3):214-219.
[36]Wilkie MJ,Smith G,Day RK,et al.2008.Polymorphisms in the SLC6A4 and HTR2A genes influence treatment outcome following antidepressant therapy[J].Pharmaco genomics J,2009,9: 61-70
[37]Ozaki N, Manji H, Lubierman V,et al. A naturally occurring amino acid substitution of the human serotonin 5-HT2A receptor influences amplitude and timing of intracellular calcium mobilization[J].J Neurochem,1997,68(5):2186-93.
[38]Hazelwood LA, Sanders-Bush E. His452Tyr polymorphism in the human 5-HT2A receptor destabilizes the signaling conformation[J].Mol Pharmacol,2004,66(5):1293-1300.
[39]Pandy SC,Piano M,Schwertz DW,et al.Effect of ethanol dependence and withdrawal on serotonin 2 receptors and phosphoinositide system in rat brain[J]Alcohol Clin Exp Res,1992,16: 392-396.
[40]LeMarquand D, Pihl RO, Benkelfat C.Serotonin and alcohol intake, abuse, and dependence: findings of animal studies[J].Biol Psychiatry,1994,36(6):395-421.
[41]LeMarquand D, Pihl RO, Benkelfat C.Serotonin and alcohol intake, abuse, and dependence: clinical evidence[J].Biol Psychiatry,1994,36(5):326-337.
[42Parsian A,Cloninger CR.Serotonergic pathway genes and subtypes of alcoholism:association studies[J].Psychiatr Genet,2001,11(2):89-94.
[43]Cloninger CR.Neurogenetic adaptive mechanisms in alcoholism[J].Science,1987,236: 410-416.
[44]Aubert R,Betoulle D,Herbeth B,et al.5-HT2A receptor gene polymorphism is associated with food and alcohol intake in obese people[J].Int J Obes Relat Metab Disord,2000,24 (7):920-924.
[45]Preuss UW,Koller G,Bondy B, et al.Impulsive traits and 5-HT2A receptor promoter polymorphism in alcohol dependents:possible association but no influence of personality disorders[J].Neuro psychobiology,2001,43:186-191.
[46]Saiz PA,Garcia-Portilla MP, Florez G,et al. Differential role of serotonergic polymorphisms in alcohol and heroin dependence[J]. Prog Neuropsychopharmacol Biol Psychiatry,2009,33:695-700.
[47]Hwu HG,Chen CH.Association of 5-HT2A receptor gene polymorphism and alcohol abuse with behavior problems[J]AmJ Med Genet,2000,96(6):797-800.
[48]仲爱芳,汪广剑,张理义.酒精依赖与5-HT2A受体基T102C多态性的相关研究[J].中华实用医学,2003,5(15)：32-33.
[49]Hill EM,Stoltenberg SF,Bullard KH,et al. Antisocial alcoholism and serotonin-related polymorphisms:association tests[J].Psychiatric Genetics,2002,12(3):143-153.
[50]Himei A,Kono Y,Yoneda H,et al. An association study between alcoholism and the serotonergic receptor genes[J].Alcohol Clin Exp Res,2000,24:341-342.
[51]Yoshihara E,Nakamura K,Itoh M,et al.2000.The human serotonin receptor gene (HTR2) Mspl polymorphism in Japanese schizophrenic and alcoholic patients[J].Neuropsychobiology,41:124-126.
[52]Schuckit MA,Mazzanti C,Smith TL,et al. Selective Genotyping for the Role of 5-HT2A, 5-HT2C and GABAa6 Receptors and the Serotonin Transporter in the Level of Response to Alcohol:A Pilot Study[J].Biol Psychiatry,1999;45:647-651
[53]Fehr C,Schleicher A,Szegedi A,et al.Serotonergic polymorphisms in patients suffering from alcoholism, anxiety disorders and narcolepsy[J]. Prog Neuro-Psychopharmacol Biol Psychiatry, 2001,25:965-982.
[54]Wojnar M,Brower KJ,Strobbe S,et al. A Association Between Val66Met Brain-Derived Neurotrophic Factor (BDNF) Gene Polymorphism and Post-Treatment Relapse in Alcohol Dependence[J].Alcohol Clin Exp Res,2009,33(4):693-702.
[55]Drago A,Liappas I,Petio C,et al. Epistasis between ILIA, IL1B, TNF, HTR2A,5-HTTLPR and TPH2 Variations Does Not Impact Alcohol Dependence Disorder Features[J].Int J Environ Res Public Health,2009,6,1980-1990.
[56]Yasseen B,Kennedy JL, Zawertailo LAet al.Comorbidity between bipolar disorder and alcohol use disorder:Association of dopamine and serotonin gene polymorphisms[J].Psychiatry Res,2010,176:30-33.
[57]Lima L.Modu laticon of 5-HT receptors in the hippocampus and the raphe arta of rats treated with clonazepam[J].Biol Psychiatry,1993,17(10):663-667.
[58]高志勤,余海鹰,刘桂永等.海洛因依赖者血小板5-羟色胺水平的观察.临床精神医学杂志,2001,11(3)：161-162.
[59]Munzar P,Justinova Z,Kutkat SW,et al.Differential involvement of 5-HT2A receptors in the discriminative-stimulus effects of cocaine and methamphetamine[J].Eur J Pharmacol,2002,436 (1-2):75-82.
[60]Saiz PA, Garcia-Portilla MP, Arango C, et al. Association between heroin dependence and 5-HT2A recep tor gene polymorphisms[J].EurAddict Res,2008,14(1):47-52.
[61]Saiz PA.Garcia-Portilla MP, Florez G,et al.Differential role of serotonergic polymorphisms in alcohol and heroin dependence[J].Prog NeuroPsychopharmacol Biol Psychiatry,2009,33:695-700.
[62]Li T, Liu X, Zhao J,et al. Allelic association analysis of the dopamine D2, D3,5-HT2A, and GABA(A) gamma2 receptors and serotonin transporter genes with heroin abuse in Chinese subjects[J].Am J Med Gent,2002,114(3):329-334.
[63]赵敏,杨德森,郝伟,等.5-TH2A受体基因1438A/G多态性与海洛因依赖的关系[J].中国药物依赖性杂志,2000,9(4)：283-284.
[64]苑成梅,赵敏,方贻儒等.海洛因依赖与52羟色胺受体基因多态性关联的研究[J].中国行为医学科学,2005,14(3)：229-231.
[65]徐振波,王廷华,张杰等.海洛因依赖与5-HTR2A基因多态性的关系[J].四川大学学报(医学版),2005,36(6)：895-896.
[66]霍塞虎.多巴胺D2受体基因及其多态性与物质依赖的相关研究[J].健康研究,2009,29(3)：214-218.
[67]汪广剑,张理义,仲爱芳等.5-羟色胺2A受体基因多态性与海洛因依赖患者的相关性研究[J].四川精神卫生,2001,14(2)：101-102.
[68]赵敏,杨德森,郝伟等.5-HT2A受体基因102T/C多态性与海洛因依赖易感性的关系[J].中国神经精神疾病杂志,2001,27(3)：224-224.
[69]Reuben M, Clarke PB.Nicotine-evoked [3H]-5-hydroxytryptamine release from rat striatal synaptosomes[J].Neuropharmacology,2000;39:290-299.
[70]Polina ER,Contini V,Hutz MH,et al.The serotonin 2A receptor gene in alcohol dependence and tobacco smoking[J].Drug,Alcohol Depend,2009,101(1-2):128-131.
[71]do Prado-Lima PA, Chatkin JM, Taufer M,et al. Polymorphism of 5HT2A serotonin receptor gene is implicated in smoking addiction [J].Am J Med Genet B Neuropsychiatr Genet,2004,128B (1):90-93.
[72]Haggstram FM, Chatkin JM, Sussenbach-Vaz E,et al.A controlled trial of nortriptyline, sustained-release bupropion and placebo for smoking cessation:preliminary results[J].Pulm Pharmacol Ther. 2006;19(3):205-209.
[73]White MJ,Young RM,Morris CP,et al.Cigarette smoking in young adults:The influence of the HTR2AT102C polymorphism and punishment sensitivity[J].Drug Alcohol Depend,2011,114: 140-146.
[2]Tyndale RF.Genetics of alcohol and tobacco use in humans[J].Ann Med,2003,35 (2),94-121.
[3]石葛明,李双成,崔慧先等.5-羟色胺转运体在酗酒人脑干头侧中缝核群的表达[J].解剖学杂志,2006,29(2)：213-215.
[4]李双成,石雄,石葛明等.酗酒与扣带回前部膝周皮质5-羟色胺转运体的表达[J].临床荟萃,2005,20(20)：1153-1155.
[5]Storvik M, Tiihonen J, Haukijarvi T,et al.Amygdala serotonin transporters in alcoholics measured by whole hemisphere autoradiography[J].Synapse,2007 61(8):629-636. [6] Storvik M, Haukijarvi T, Tupala E,et al.Correlation between the SERT binding densities in hypothalamus and amygdala in Cloninger type 1 and 2 alcoholics[J].Alcohol,2005,43(1):25-30.
[7]Underwood MD, Mann JJ, Huang YY, et al. Family history of alcoholism is associated with lower 5-HT2A receptor binding in the prefrontal cortex[J].Alcohol Clin Exp Res,2008, 32:593-599.
[8]Agarwal DP.Molecular genetic aspects of alcohol metabolism and alcoholism[J]. Pharmaco psychiatry,1997,30(3):79-84.
[9]Chen WJ,Loh E-W,Hsu Y-PP,et al.Alcohol-metabolising genes and alcoholism among Taiwanese Hanmen:independent effect of ADH2,ADH3, and ALDH2[J].Br J Psychiatry, 1996b,168(6):762-767.
[10]Maezawa Y,Yamauchi M,Suzuki TG,et al.Alcohol-metabolizing enzyme polymerphisms and alcoholism in Japan[J].Alcohol Clin Exp Res,1995,19(4):951-954.
[ll]Muramatsu T,Wang ZC,Fang YR, et al.Alcohol and aldehyde dehydrogenase genotypes and drinking behavior of Chinese living in Shanghai[J].Hum Genet,1995,96(2):151-154.
[12]Nakamura K,Iwahashi K,Matsuo Y,et al.Characteristics of Japanese alcoholics with the atypical aldehyde dehydrogenase 2*2.I. A comparison of the genotypes of ALDH2VADH2, ADH3, and cytochrome P-4502E1 between alcoholics and nonalcoholics[J].Alcohol Clin Exp Res,1996, 20(1):52-55.
[13]Shen YC,Fan JH,Edenberg HJ,et al.Polymorphism of ADH and ALDH genes among four ethnic groups in China and effects upon the risk for alcoholism[J]. Alcohol Clin Exp Res,1997, 21(7):1272-1277.
[14]Lee HC,Lee HS,Jung S-H,et al.Association between polymorphisms of ethanol-metabolizing enzymes and susceptibility to alcoholic cirrhosis in a Korean male population[J].J Korean Med Sci,2001,16(6):745-750.
[15]Yasunami M,Kikuchi I,Sarapata D,et al.The human class Ⅰ alcohol dehydrogenase gene cluster:three genes are tandemly organized in an 80-kb-long segment of the genome[J].Genomics, 1990,7(2):152-158.
[16]贺艮峰.酒精依赖综合征与ADH2、CYP4502E1基因多态性的相关研究.云南昆明：昆明医学院,2008
[17]高丽波,钟树荣,景强等.云南汉族酒精依赖综合征与ADH2、ALDH2基因多态性的关联研究[J],医学研究杂志,2010,39(3)：35-39.
[18]Lucki I.The spectrum of behaviors influenced by serotonin.Biol Psychiatry,1998,44:151-162.
[19]Veenstra-VanderWeele J,Anderson GM,Cook EH Jr.Pharmacogenetics and the serotonin systemrinitial studies and future directions[J].Eur J Pharmacol,2000,410:165-181.
[20]Gingrich JA, Ansorge MS,Merker R,et al.New lessons from knockout mice:The role of serotonin during development and its possible contribution to the origins of neuropsychiatric disorders[J].CNS Spectr.2003;8:572-7.
[21]Fisher PM,Munoz KE,Hariri AR.Identification of neurogenetic pathways of risk for psychopathology[J]. Am J Med Genet C Semin Med Genet,,2008,2:147'-153.
[22]D'Souza UM,Craig IW.Functional polymorphisms in dopamine and serotonin pathway genes[J].Hum Mutat,2006,1:1-13.
[23]Norton N and Owen MJ.HTR2A:Association and expression studies in neuropsychiatric Genelics[J] Annals of Medicine,2005,31:121-129.
[24]Pandy SC,Piano M,Schwertz DW,et al.Effect of ethanol dependence and withdrawal on serotonin 2 receptors and phosphoinositide system in rat brain[J]Alcohol Clin Exp Res,1992,16: 392-396.
[25]LeMarquand D, Pihl RO, Benkelfat C.Serotonin and alcohol intake, abuse, and dependence: findings of animal studies[J].Biol Psychiatry,1994,36(6):395-421.
[26]LeMarquand D, Pihl RO, Benkelfat C.Serotonin and alcohol intake, abuse, and dependence: clinical evidence[J].Biol Psychiatry,1994,36(5):326-337.
[27]Lesch KP.Alcohol dependence and gene x environment interaction in emotion regulation:Is serotonin the link[J]? Eur J Pharmacol,2005,1:113-124.
[28]Vengeliene V,BilbaoA,Molander A,et al.Neuropharmacology of alcohol addiction[J].Br J Pharmacol,2008,2:299-315.
[29]Bowirrat A and Oscar-Berman M. Relationship between dopaminergic neurotransmission, alcoholism, and Reward Deficiency syndrome[J]. Am J Med Genet B Neuropsychiatr Genet. 2005,132B(1):29-37.
[30]Bunney EB,Appel SB,Brodie MS.Cocaine potentiates ethanol-induced excitation of dopaminergic reward neurons in the ventral tegmental area[J].J Pharmacol Exp Ther, 2000,293(2):383-390.
[31]Nocjarc C,Roth BL,Pehek A.Localization of 5-HT2Areceptors on dopamine cells in subnuclei of the midbrain A10 cell group[J].Neurosci,2002,111(1):163-178.
[32]Marques FZ, Hutz MH, Bau CH. Influence of the serotonin transporter gene on comorbid disorders among alcohol-dependent individuals[J].Psychiatr Gene,2006,16(3):125-131
[33]Gorwood P, Batel P, Ades J, Hamon M, Boni C.Serotonin transporter gene polymorphisms, alcoholism, and suicidal behavior[J].Biol Psychiatry,2000,48(4):259-264.
[34]Sellers EM, Higgins GA, Sobell MB.5-HT and alcohol abuse[J].TIPS,1992,13:69-75.
[35]Higuchi S, Suzuki K, Yamada K,et al.Alcoholics with eating disorders:prevalence and clinical course:a study fromJapan[J].Br J Psychiatry,1993,162:403-406.
[36]Chen K,Yang W,Grimsby J,et al.The human 5HT2A receptor is encoded by a multiple intron-exon gene[J].Brain Res Mol Brain Res,1992,14:20-26.
[37]Parsons MJ,D'Souza UM, Arranz MJ,et al.The-1438A/G polymorphism in the 5-hydroxytryptamine type 2A receptor gene affects promoter activity[J].Biol Psychiatry,2004,56: 406-410.
[38]Spurlock G,Heils A,Holmans P,et al.A family based association study of T102C polymorphism in 5HT2A and schizophrenia plus identification of new polymorphisms in the promoter[J]. Mol Psychiatry,1998,3:42-49.
[39]Kouzmenko AP,Scaffidi A,Pereira AM,et al.No correlation between A(-1438)G polymorphism in 5-HT2A receptor gene promoter and the density of frontal cortical 5-HT2A receptors in schizophrenia[J].Hum Hered,1999,49:103-105.
[40]Arranz MJ,Munro J,Birkett J,et al.Pharmacogenetic prediction of clozapine response[J]. Lancet,2000,355:1615-1616.
[41]Kusumi I,Suzuki K,Sasaki Y,et al.Serotonin5-HT(2A) receptor gene polymorphism,5-HT(2A) receptor function and personality traits in healthy subjects:A negative study[J].JAffect Disord, 2002,68:235-241.
[42]Bray NJ,Buckland PR,Hall H,et al.The serotonin-2A receptor gene locus does not contain common polymorphism affecting mRNA levels in adult brain[J].Mol Psychiatry,2004,9:109-114.
[43]Mata I,Arranz MJ,Patino A,et al.Serotonergic polymorphisms and psychotic disorders in populations from North Spain[J].Am J Med Genet B Neuropsychiatr Genet,2004,126:88-94.
[44]Martinez-Barrondo S,Saiz PA,Morales B,et al.Serotonin gene polymorphisms in patients with panic disorder[J].Actas Esp Psiquiatr,2005,33:210-216.
[45]Saiz PA,Garcia-Portilla MP,Arango C,et al.Association study of serotonin 2Areceptor (5-HT2A) and serotonin transporter(5-HTT) gene polymorphisms with schizophrenia[J].Prog Neuropsychopharmacol Biol Psychiatry,2001,31:741-745.
[46]Nielsen K,Brask D,Knudsen GM, et al.Immunodetection of the serotonin transporter protein is a more valid marker for serotonergic fibers than serotonin[J].Synapse,2006,59(5):270-276
[47]Lesch KP,Balling U,Gross J,et al.Organization of the human serotonin transporter gene[J].J Neural Transm Gen Sect,1994,95(2):157-162.
[48]Hranilovic D,Stefulj J,Schwab S,et al.Serotonin transporter promoter and intron 2 polymorphisms:relationship between allelic variants and gene expression[J].Biol Psychiatry, 2004,55(11):1090-1094.
[49]Heils A,Teufel A,Petri S,et al.Allelic variation of human serotonin transporter gene expression[J].J Neurochem,1996,66(6):2621-2624.
[50]Greenberg BD,Tolliver T J,Huang S J,et al.Genetic variation in the serotonin transporter promoter region affects serotonin uptake in human blood platelets[J]. Am J Med Genet,1999, 88(1):83-87.
[51]Reimold M, Smolka MN, Schumann G,et al.Midbrain serotonin transporter binding potential measured with [11C]DASB is affected by serotonin transporter genotype[J]. J Neural Transm, 2007,114(5):635-639.
[52]Bradley SL,Dodelzon K,Sandhu HK,et al.Relationship of serotonin transporter gene polymorphisms and haplotypes to mRNA transcription[J].Am J Med Genet B Neuropsychiatr Genet,2005,136B(1):58-61.
[53]Philibert RA,Sandhu H,Hollenbeck N,et al.The relationship of 5HTT (SLC6A4) methylation and genotype on mRNA expression and liability to major depression and alcohol dependence in subjects from the Iowa Adoption Studies[J].Am J Med Genet B Neuropsychiatr Genet,2008, 147B(5):543-549.
[54]吴艳茹,肖泽萍,禹顺英,范娟,汪栋祥.5-羟色胺转运体启动子基因多态与青少年抑郁症患者人格特质的关联研究[J].中国神经精神疾病杂志,2009,35(4)：234-237.
[55]Gokturk C,Schultze S,Nilsson KW,et al.Serotonin transporter (5-HTTLPR) and monoamine oxidase (MAOA) promoter polymorphisms in women with severe alcoholism[J].Arch Womens Ment Health,2008,11(5-6):341-355.
[56]Thompson MD,Gonzalez N,Nguyen T,et al. Serotonin transporter gene polymorphisms in alcohol dependence[J].Alchohol,2000,22(2):61-67.
[57]Konishi T,Luo HR,Calvillo M,et al.ADH1B*1, ADH1C*2, DRD2 (-141C Ins), and 5-HTTLPR are associated with alcoholism in Mexican American men living in Los Angeles[J]. Alcohol Clin Exp Res,2004,28(8):1145-1152.
[58]K6hnke MD,Kolb W,Lutz U,et al.The serotonin transporter promotor polymorphism 5-HTTLPR is not associated with alcoholism or severe forms of alcohol withdrawal in a German sample[J].Psychiatr Genet,2006,16(6):227-228.
[59]Gorwood P, Lanfumey L, Hamon M. Alcohol dependence and polymorphisms of serotonin-related genes[J].Med Sci (Paris),2004,20(12):1132-1138.
[60]Hallikainen T,Saito T,Lachman HM,et al.Association between low activity serotonin transporter promoter genotype and early onset alcoholism with habitual impulsive violent behavior[J].Mol Psychiatry,1999,4(4):385-388.
[61]Matsushita S,Yoshino A,Murayama M,et al.Association study of serotonin transporter gene regulatory region polymorphism and alcoholism[J]. Am J Med Genet,2001 Jul 8;105(5):446-450.
[62]Lee YS, Choi SW, Han DH,et al.Clinical manifestation of alcohol withdrawal symptoms related to genetic polymorphisms of two serotonin receptors and serotonin transporter[J].Eur Addict Res,2009,15(1):39-46.
[63]严卫丽.复杂疾病全基因组关联研究进展—遗传统计分析[J].遗传2008(05)：543-549.
[64]Myers RL,Airey DC,Manier DH,et al.Polymorphisms in the regulatory region of the human serotonin 5-HT2A receptor gene (HTR2A) influence gene expression[J].Bio Psychiatry,2007, 61:167-173.
[65]Nakamura T,Matsushita S,Nishiguchi N,et al.Association of a polymorphismof the 5HT2A receptor gene promoter region with alcohol dependence[J].Mol Psychiatry,1999,4:85-88.
[66]Parsian A,Cloninger CR.Serotonergic pathway genes and subtypes of alcoholism:association studies[J].Psychiatr Genet,2001,11(2):89-94.
[67]Cloninger CR.Neurogenetic adaptive mechanisms in alcoholism.Science,1987,236:410-416.
[68]Aubert R,Betoulle D,Herbeth B,et al.5-HT2A receptor gene polymorphism is associated with food and alcohol intake in obese people[J].Int J Obes Relat Metab Disord,2000,24 (7):920-924.
[69]Polina ER,Contini V,Hutz MH,et al.The serotonin 2A receptor gene in alcohol dependence and tobacco smoking[J].Drug Alcohol Depend,2009,101,128-131.
[70]Preuss UW,Koller G,Bondy B, et al.Impulsive traits and 5-HT2A receptor promoter polymorphism in alcohol dependents:possible association but no influence of personality disoTdeis[J].Neuro psychobiology,2001,43,186-191.
[71]曹莉萍,李涛,许珂等.海洛因依赖与5-HT2A受体基因-1438A/G多态性的相关研究[J].中国药物依赖性杂志,2002,11(4)：266-268
[72]邵春红,江开达,李一峰.5-羟色胺2A受体基因多态与海洛因成瘾渴求程度的关联分析[J].中国神经精神疾病杂志,2005,31(5):321-325.
[73]张英,刘盈.5-HTR2A基因-1438A/G多态性与重性抑郁障碍药效学作用的关联研究[J].辽宁沈阳：中国医科大学,2008.
[74]喻妍,赵靖平,吴仁容等.5-羟色胺2A受体基因-1438A/G多态性与抑郁症的关联研究[J].国际精神病学杂志,2009,36(2)：65-68.
[75]Guhathakurta S,Singh AS,Sinha S,et al.Analysis of serotonin receptor 2Agene (HTR2A): Association study with autism spectrum disorder in the Indian population and investigation of the gene expression in peripheral blood leukocytes[J]. Neurochem Int,2009,55:754-759
[76]Zoroglu SS,Erdal ME,Erdal N,et al.No evidence for an association between the T102C and 1438G/A polymorphisms of the serotonin 2A receptor gene in attention deficit/hyperactivity disorder in a Turkish population[J].Biol Psychiatry,2003,47:17-20.
[77]Enoch MA,Kaye WH,Rotondo A,et al.5-HT2A promoter polymorphism-1438 G/A, anorexia nervosa,and obsessive-compulsive disorder[J].Lancet,1998,351:1785-1786.
[786]Hinney A,Remschmidt H,Hebebrand J.Candidate gene polymorphisms in eating disorders[J]. Eur J Pharmacol,2000,410:147-159.
[79]Saiz PA,Garcia-Portilla MP, Arango C,et al.2008. Association study between obsessive-compulsive disorder and serotonergic candidate genes[J].Prog Neuropsychopharmacol Biol Psychiatry,32:165-770.
[80]Sorli JV, Frances F,Gonzolez JI,et al.Impact of the-1438G>A polymorphism in the serotonin 2A receptor gene on anthropometric profile and obesity risk:a case-control study in a Spanish Mediterranean population[J].Appetite,2008,50:260-265.
[81]Saiz PA,Garcia-Portilla MP, Florez G,et al. Differential role of serotonergic polymorphisms in alcohol and heroin dependence[J].Prog Neuropsychopharmacol Biol Psychiatry,2009,33:695-700.
[82]Turecki G,Briere R,Dewar K,et al.Prediction of level of serotonin 2A receptor binding by serotonin receptor 2A genetic variation in postmortem brain samples from subjectswho did or did not commit suicide[J].Am J Psychiatry,1999,156:1456-1458.
[83]Khait VD,Huang YY,Zalsman G,et al.Association of serotonin 5-HT2A receptor binding and the T102C polymorphism in depressed and healthy Caucasian subjects[J].NeuroPsychoPharmaco-logy,2005,30:166-112.
[84]Polesskaya OO,Sokolov BP.Differential expression of the "C" and "T"alleles of the 5-HT2A receptor gene in the temporal cortex of normal individuals and schizophrenics[J].J Neurosici Res 2002,67:812-822.
[85]Lane HY,Chang YC,Chiu CC et al. Association of risperidone treatment response with a polymorphism in the 5-HT(2A) receptor gene[J].Am J Psychiatry,2002,159:1593-1595.
[86]Du L,Faludi G,Palkovits M, et al.Frequency of long allele in serotonin transporter gene is increased in depressed suicide victims[J].Biol Psychiatry,1999,46:196-201.
[87]Kouzmenko AP,Hayes WL,Pereira AM,et al.5-HT2A receptor polymorphism and steady state receptor expression in schizophrenia[J].Lancet,1997,349:1815-1820.
[88]Kouzmenko AP,Scaffidi A,Pereira AM,et al.No correlation between A(-1438)G polymorphism in 5-HT2A receptor gene promoter and the density of frontal cortical 5-HT2A receptors in schizophrenia[J].Hum Hered,1999,49:103-105.
[89]Bray NJ,Buckland PR,Hall H,et al.The serotonin-2A receptor gene locus does not contain common polymorphism affecting mRNA levels in adult brain.Mol Psychiatry,2004,9:109-114
[90]Hwu HG,Chen CH,Association of 5-HT2A receptor gene polymorphism and alcohol abuse with behavior problems[J].AmJ Med Genet,2000,96(6):797-800.
[91]仲爱芳,汪广剑,张理义.酒精依赖与5-HT2A受体基T102C多态性的相关研究[J].中华实用医学,2003,5(15)：32-33.
[92]Hill EM,Stoltenberg SF,Bullard KH,et al. Antisocial alcoholism and serotonin-related polymorphisms:association tests[J].Psychiatric Genetics,2002,12(3):143-153.
[93]Himei A,Kono Y,Yoneda H,et al. An association study between alcoholism and the serotonergic receptor genes[J]. Alcohol Clin Exp Res,2000,24:341-342.
[94]Yoshihara E,Nakamura K,Itoh M,et al.2000.The human serotonin receptor gene (HTR2) Mspl polymorphism in Japanese schizophrenic and alcoholic patients[J].Neuropsychobiology,41:124-126.
[95]Schuckit MA,Mazzanti C,Smith TL,et al. Selective Genotyping for the Role of 5-HT2A, 5-HT2C and GABAa6 Receptors and the Serotonin Transporter in the Level of Response to Alcohol:A Pilot Study[J].Biol Psychiary,1999;45:647-651
[96]Fehr C,Schleicher A,Szegedi A,et al.Serotonergic polymorphisms in patients suffering from alcoholism, anxiety disorders and narcolepsy[J].Prog Neuropsychopharmacol Biol Psychiatry, 2001,25:965-982.
[97]Wojnar M,Brower KJ,Strobbe S,et al.A Association Between Val66Met Brain-Derived Neurotrophic Factor (BDNF) Gene Polymorphism and Post-Treatment Relapse in Alcohol Dependence[J].Alcohol Clin Exp Res,2009,33(4):693-702.
[98]Drago A,Liappas I,Petio C,et al. Epistasis between ILIA, IL1B, TNF, HTR2A,5-HTTLPR and TPH2 Variations Does Not Impact Alcohol Dependence Disorder Features[J].Int J Environ Res Public Health,2009,6,1980-1990.
[99]Choi JH, Zhang SY, Park KW,et al.The Association between the T102C Polymorphism of the HTR2A Serotonin Receptor Gene and HDL Cholesterol Level in Koreans[J].J Biochem Mol Biol, 2005,38, (2):238-242
[100]Bondy B,Kuznik Jbaghai T,et al.Lack of association of serotonin-2A receptor gene polymorphism (T102C) with suicidal ideation and suicide[J].Am. JMed Genet,2000,96,831-835.
[101]Yu BN,Wang A,Zhou G,et al.T102C genetic polymorphism of the 5-HT2A receptor in Chinese hypertensive patients and healthy controls[J].Clin Exp Pharmacol Physiol,2004,31, 847-849.
[102]Ozaki N, Manji H, Lubierman V,et al. A naturally occurring amino acid substitution of the human serotonin 5-HT2A receptor influences amplitude and timing of intracellular calcium mobilization[J].J Neurochem,1997,68(5):2186-93.
[103]Hazelwood LA, Sanders-Bush E. His452Tyr polymorphism in the human 5-HT2A receptor destabilizes the signaling conformation[J].Mol Pharmacol,2004,66(5):1293-1300.
[104]Yasseen B,Kennedy JL, Zawertailo LA et al.Comorbidity between bipolar disorder and alcohol use disorder:Association of dopamine and serotonin gene polymorphisms[J].Psychiatry Res,2010,176:30-33.
[105]Guhathakurta S,Singh AS,Sinha S,et al.Analysis of serotonin receptor 2A gene (HTR2A): Association study with autism spectrum disorder in the Indian population and investigation of the gene expression in peripheral blood leukocytes[J].Neurochem Int,2009,55:754-759.
[106]Ni X,Bismil R,Chan K,et al. Serotonin 2A receptor gene is associated with personality traits, but not to disorder, in patients with borderline personality disorder[J]. Neurosci Lett,2006,408: 214-219.
[107]Wilkie MJ,Smith G,Day RK,et al.2008. Polymorphisms in the SLC6A4 and HTR2A genes influence treatment outcome following antidepressant therapy[J].Pharmaco genomics J,2009,9: 61-70
[108]Kan JL,Green MR.Pre-mRNA splicing of IgM exons M1 and M2 is directed by a juxtaposed splicing enhancer and inhibitor[J].Genes Dev,1999,13(4):462-471.
[109]Brockmoller J,Cascorbi I,Kerb R,et al.Polymorphisms in xenobiotic conjugation and disease predisposition[J].Toxicol Lett,1998,102-103:173-183.
[110]Excoffier L,Slatkin M.Maximum-likelihood estimation of molecular haplotype frequencies in a diploid population[J]. Mol Biol Evol,1995,12(5):921-927.
[111]Rioux JD,Daly MJ,Silverberg MS,et al.Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease[J].Nat Genet,2001,29:223-228.
[112]高树贵,刘少文,蔡贵庆等.5-羟色胺转运体基因启动子区与心境障碍的关联分析[J].上海精神医学,2004,16(3)：141-144.
[113]唐牟尼,李涛,刘协和等.载脂蛋白E、5-羟色胺转运体基因多态性与阿尔茨海默病的关联分析[J].中华精神科杂志,2000,33(3)：145-148.
[114]Hammoumi S, Payen A, Favre JD, Balmes JL, Benard JY, Husson M, Ferrand JP, Martin JP, Daoust M.Does the short variant of the serotonin transporter linked polymorphic region constitute a marker of alcohol dependence[J]? Alcohol,1999,17(2):107-112.
[115]Lichtermann D, Hranilovic D, Trixler M, Franke P, Jernej B, Delmo CD, Knapp M, Schwab SG, Maier W, Wildenauer DB. Support for allelic association of a polymorphic site in the promoter region of the serotonin transporter gene with risk for alcohol dependence[J].Am J Psychiatry,2000, 157(12):2045-2047.
[116]Kranzler H, Lappalainen J, Nellissery M, Gelernter J. Association study of alcoholism subtypes with a functional promoter polymorphism in the serotonin transporter protein gene[J]. Alcohol Clin Exp Res,2002,26(9):1330-1335.
[117]Foley PF, Loh EW, Innes DJ, Williams SM, Tannenberg AE, Harper CG, Dodd PR.Association studies of neurotransmitter gene polymorphisms in alcoholic Caucasians[J].Ann N YAcad Sci,2004,1025:39-46.
[118]Feinn R, Nellissery M, Kranzler HR. Meta-analysis of the association of a functional serotonin transporter promoter polymorphism with alcohol dependence[J].Am J Med Genet B Neuropsychiatr Genet,2005,133B(1):79-84.
[119]McHugh RK, Hofmann SG, Asnaani A, Sawyer AT, Otto MW. The serotonin transporter gene and risk for alcohol dependence:a meta-analytic review[J]. Drug AlcoholDepend,2010,108(1-2): 1-6.
[120]Saiz PA, Garcia-Portilla MP, Arango C, et al. Association between heroin dependence and 5-HT2A recep tor gene polymorphisms[J].Eur Addict Res,2008,14 (1):47-52.
[121]李恒芬.5-HT信号传导相关SNPs与心境障碍.云南昆明：中南大学,2008.
[122]武颖.5-HT传导通路相关基因多态性与重性抑郁症的关联性研究.山西太原：山西医科大学,2008.
[1]Tsuang MT,Bar JL,Harley RM,et al.The Harvard Twin Study of Substance Abuse:what we have learned[J].Harv Rev Psychiatry,2001,9:267-279.
[2]Shih RA,Belmonte PL,Zandi PP.A review of the evidence from family, twin and adoption studies for a genetic contribution to adult psychiatric disorders[J].Int Rev Psychiatry,2004,16 (4):260-283.
[3]Uhl GR, Drgon T, Johnson C,et al.Higher order addiction molecular genetics:Convergent data from genome-wide association in humans and mice[J].Biochem Pharmacol,2008,75:98-111.
[4]Filip M, Frankowska M, Zaniewska M,et al.The serotonergic system and its role in cocaine addiction[J].Pharmacol Rep,2005,57:685-700.
[5]Higgins GA,Fletcher PJ.Serotonin and drug reward:focus on 5-HT 2C receptors[J].Eur J Pharmacol,2003,480:151-162.
[6]Johnson BA:Role of the serotonergic system in the neurobiology of alcoholism:implications for treatment[J].CNS Drugs,2004,18:1105-1118.
[7]Lucki I.The spectrum of behaviors influenced by serotonin[J].Biol Psychiatry,1998,44: 151-162.
[8]Veenstra-VanderWeele J,Anderson GM,Cook EH Jr.Pharmacogenetics and the serotonin system:initial studies and future directions[J].Eur J Pharmacol,2000,410:165-181.
[9]Gingrich JA, Ansorge MS,Merker R,et al.New lessons from knockout mice:The role of serotonin during development and its possible contribution to the origins of neuropsychiatric disorders[J].CNS Spectr.2003;8:572-7.
[10]Sills TL,Fletcker PJ.Fluoxetine attenuates morphine-induced locomotion and blocks morphine-sensitization[J].Eur J Pharmacol,1997,337:161-164.
[11]Parsons LH,Koob GF,Weiss F.Serotonin dysfunction in the nucleus accumbens of rats during withdrawal after unlimited access to intravenous cocaine[J].J Pharmacol ExpTher,1995,274:1182-1187.
[12]Little KY,Patel UN,Clark TB,et al.Alteration of brain dopamine and serotonin levels in cocaine users:a prekuminary report [J]. Am J Psychiatry,1996,153(9):1216-1218.
[13]Bowirrat A and Oscar-Berman M. Relationship between dopaminergic neurotransmission, alcoholism, and Reward Deficiency syndrome[J]. Am J Med Genet B Neuropsychiatr Gene,. 2005,132B(1):29-37.
[14]DackisC,Brien C.Neurobiology of addiction:treatment and public policy ramifications[J]. Nat Neurosci,2005,8:1431-1436.
[15]王学铭.精神与精神病的生物化学[M].北京：人民卫生出版社,2002,268-269
[16]Chen K,Yang W,Grimsby J,et al.The human 5HT2A receptor is encoded by a multiple intron-exon gene[J].Brain Res Mol Brain Res,1992,14:20-26.
[17]Parsons MJ,D'Souza UM, Arranz MJ,et al.The-1438A/G polymorphism in the 5-hydroxy- tryptamine type 2A receptor gene affects promoter activity[J].Biol Psychiatry,2004,56:406-410.
[18]Nakamura T,Matsushita S,Nishiguchi N,et al.Association of a polymorphismof the 5HT2A receptor gene promoter region with alcohol dependence[J].Mol Psychiatry,1999,4:85-88.
[19]曹莉萍,李涛,许珂等.海洛因依赖与5-HT2A受体基因-1438A/G多态性的相关研究[J].中国药物依赖性杂志,2002,11(4):266-268
[20]邵春红,江开达,李一峰.5-羟色胺2A受体基因多态与海洛因成瘾渴求程度的关联分析[J].中国神经精神疾病杂志,2005,31(5):321-325.
[21]张英,刘盈.5-HTR2A基因-1438A/G多态性与重性抑郁障碍药效学作用的关联研究[J].辽宁沈阳：中国医科大学,2008.
[22]喻妍,赵靖平,吴仁容等.5-羟色胺2A受体基因-1438A/G多态性与抑郁症的关联研究[J].国际精神病学杂志,2009,36(2):65-68.
[23]Guhathakurta S,Singh AS,Sinha S,et al.Analysis of serotonin receptor 2A gene (HTR2A): Association study with autism spectrum disorder in the Indian population and investigation of the gene expression in peripheral blood leukocytes[J]. Neurochem Int,2009,55(8):754-759
[24]Zoroglu SS,Erdal ME,Erdal N,et al.No evidence for an association between the T102C and 1438G/A polymorphisms of the serotonin 2A receptor gene in attention deficit/hyperactivity disorder in a Turkish population[J].Biol Psychiatry,2003,47:17-20.
[25]Enoch MA,Kaye WH,Rotondo A,et al.5-HT2A promoter polymorphism-1438 G/A, anorexia nervosa,and obsessive-compulsive disorder[J].Lancet,1998,351 (9118):1785-1786.
[26]Hinney A,Remschmidt H,Hebebrand J.Candidate gene polymorphisms in eating disorders[J]. Eur J Pharmacol,2000,410:147-159.
[27]Saiz PA,Garcia-Portilla MP, Arango C,et al.2008. Association study between obsessive-compulsive disorder and serotonergic candidate genes[J]. Prog Neuropsychopharmacol Biol Psychiatry,32:765-770.
[28]Sorli JV, Frances F,Gonzalez JI,et al.Impact of the-1438G>A polymorphism in the serotonin 2A receptor gene on anthropometric profile and obesity risk:a case-control study in a Spanish Mediterranean population[J].Appetite,2008,50:260-265.
[29]Choi JH, Zhang SY, Park KW,et al.The Association between the T102C Polymorphism of the HTR2A Serotonin Receptor Gene and HDL Cholesterol Level in Koreans[J]. J Biochem Mol Biol, 2005,38(2):238-242
[30]Bondy B,Kuznik Jbaghai T,et al.Lack of association of serotonin-2A receptor gene polymorphism (T102C) with suicidal ideation and suicide[J].Am J Med Genet,2000,96,831-835.
[31]Yu BN,Wang A,Zhou G,et al.T102C genetic polymorphism of the 5-HT2A receptor in Chinese hypertensive patients and healthy controls[J].Clin Exp Pharmacol Physiol,2004,31,847-849.
[32]Fehr C,Schleicher A,Szegedi A,et al.Serotonergic polymorphisms in patients suffering from alcoholism, anxiety disorders and narcolepsy[J].Prog Neuropsychopharmacol Biol Psychiatry, 2001,25:965-982.
[33]Wojnar M,Brower KJ,Strobbe S,et al.A Association Between Va166Met Brain-Derived Neurotrophic Factor (BDNF) Gene Polymorphism and Post-Treatment Relapse in Alcohol Dependence[J].Alcohol Clin ExpRes,2009,33(4):693-702.
[34]Guhathakurta S,Singh AS,Sinha S,et al.Analysis of serotonin receptor 2A gene (HTR2A): Association study with autism spectrum disorder in the Indian population and investigation of the gene expression in peripheral blood leukocytes[J].Neurochem Int,2009,55:754-759.
[35]Ni X,Bismil R,Chan K,et al.Serotonin 2A receptor gene is associated with personality traits, but not to disorder, in patients with borderline personality disorder[J].Neurosci Lett,2006, 408(3):214-219.
[36]Wilkie MJ,Smith G,Day RK,et al.2008.Polymorphisms in the SLC6A4 and HTR2A genes influence treatment outcome following antidepressant therapy[J].Pharmaco genomics J,2009,9: 61-70
[37]Ozaki N, Manji H, Lubierman V,et al. A naturally occurring amino acid substitution of the human serotonin 5-HT2A receptor influences amplitude and timing of intracellular calcium mobilization[J].J Neurochem,1997,68(5):2186-93.
[38]Hazelwood LA, Sanders-Bush E. His452Tyr polymorphism in the human 5-HT2A receptor destabilizes the signaling conformation[J].Mol Pharmacol,2004,66(5):1293-1300.
[39]Pandy SC,Piano M,Schwertz DW,et al.Effect of ethanol dependence and withdrawal on serotonin 2 receptors and phosphoinositide system in rat brain[J]Alcohol Clin Exp Res,1992,16: 392-396.
[40]LeMarquand D, Pihl RO, Benkelfat C.Serotonin and alcohol intake, abuse, and dependence: findings of animal studies[J].Biol Psychiatry,1994,36(6):395-421.
[41]LeMarquand D, Pihl RO, Benkelfat C.Serotonin and alcohol intake, abuse, and dependence: clinical evidence[J].Biol Psychiatry,1994,36(5):326-337.
[42Parsian A,Cloninger CR.Serotonergic pathway genes and subtypes of alcoholism:association studies[J].Psychiatr Genet,2001,11(2):89-94.
[43]Cloninger CR.Neurogenetic adaptive mechanisms in alcoholism[J].Science,1987,236: 410-416.
[44]Aubert R,Betoulle D,Herbeth B,et al.5-HT2A receptor gene polymorphism is associated with food and alcohol intake in obese people[J].Int J Obes Relat Metab Disord,2000,24 (7):920-924.
[45]Preuss UW,Koller G,Bondy B, et al.Impulsive traits and 5-HT2A receptor promoter polymorphism in alcohol dependents:possible association but no influence of personality disorders[J].Neuro psychobiology,2001,43:186-191.
[46]Saiz PA,Garcia-Portilla MP, Florez G,et al. Differential role of serotonergic polymorphisms in alcohol and heroin dependence[J]. Prog Neuropsychopharmacol Biol Psychiatry,2009,33:695-700.
[47]Hwu HG,Chen CH.Association of 5-HT2A receptor gene polymorphism and alcohol abuse with behavior problems[J]AmJ Med Genet,2000,96(6):797-800.
[48]仲爱芳,汪广剑,张理义.酒精依赖与5-HT2A受体基T102C多态性的相关研究[J].中华实用医学,2003,5(15)：32-33.
[49]Hill EM,Stoltenberg SF,Bullard KH,et al. Antisocial alcoholism and serotonin-related polymorphisms:association tests[J].Psychiatric Genetics,2002,12(3):143-153.
[50]Himei A,Kono Y,Yoneda H,et al. An association study between alcoholism and the serotonergic receptor genes[J].Alcohol Clin Exp Res,2000,24:341-342.
[51]Yoshihara E,Nakamura K,Itoh M,et al.2000.The human serotonin receptor gene (HTR2) Mspl polymorphism in Japanese schizophrenic and alcoholic patients[J].Neuropsychobiology,41:124-126.
[52]Schuckit MA,Mazzanti C,Smith TL,et al. Selective Genotyping for the Role of 5-HT2A, 5-HT2C and GABAa6 Receptors and the Serotonin Transporter in the Level of Response to Alcohol:A Pilot Study[J].Biol Psychiatry,1999;45:647-651
[53]Fehr C,Schleicher A,Szegedi A,et al.Serotonergic polymorphisms in patients suffering from alcoholism, anxiety disorders and narcolepsy[J]. Prog Neuro-Psychopharmacol Biol Psychiatry, 2001,25:965-982.
[54]Wojnar M,Brower KJ,Strobbe S,et al. A Association Between Val66Met Brain-Derived Neurotrophic Factor (BDNF) Gene Polymorphism and Post-Treatment Relapse in Alcohol Dependence[J].Alcohol Clin Exp Res,2009,33(4):693-702.
[55]Drago A,Liappas I,Petio C,et al. Epistasis between ILIA, IL1B, TNF, HTR2A,5-HTTLPR and TPH2 Variations Does Not Impact Alcohol Dependence Disorder Features[J].Int J Environ Res Public Health,2009,6,1980-1990.
[56]Yasseen B,Kennedy JL, Zawertailo LAet al.Comorbidity between bipolar disorder and alcohol use disorder:Association of dopamine and serotonin gene polymorphisms[J].Psychiatry Res,2010,176:30-33.
[57]Lima L.Modu laticon of 5-HT receptors in the hippocampus and the raphe arta of rats treated with clonazepam[J].Biol Psychiatry,1993,17(10):663-667.
[58]高志勤,余海鹰,刘桂永等.海洛因依赖者血小板5-羟色胺水平的观察.临床精神医学杂志,2001,11(3)：161-162.
[59]Munzar P,Justinova Z,Kutkat SW,et al.Differential involvement of 5-HT2A receptors in the discriminative-stimulus effects of cocaine and methamphetamine[J].Eur J Pharmacol,2002,436 (1-2):75-82.
[60]Saiz PA, Garcia-Portilla MP, Arango C, et al. Association between heroin dependence and 5-HT2A recep tor gene polymorphisms[J].EurAddict Res,2008,14(1):47-52.
[61]Saiz PA.Garcia-Portilla MP, Florez G,et al.Differential role of serotonergic polymorphisms in alcohol and heroin dependence[J].Prog NeuroPsychopharmacol Biol Psychiatry,2009,33:695-700.
[62]Li T, Liu X, Zhao J,et al. Allelic association analysis of the dopamine D2, D3,5-HT2A, and GABA(A) gamma2 receptors and serotonin transporter genes with heroin abuse in Chinese subjects[J].Am J Med Gent,2002,114(3):329-334.
[63]赵敏,杨德森,郝伟,等.5-TH2A受体基因1438A/G多态性与海洛因依赖的关系[J].中国药物依赖性杂志,2000,9(4)：283-284.
[64]苑成梅,赵敏,方贻儒等.海洛因依赖与52羟色胺受体基因多态性关联的研究[J].中国行为医学科学,2005,14(3)：229-231.
[65]徐振波,王廷华,张杰等.海洛因依赖与5-HTR2A基因多态性的关系[J].四川大学学报(医学版),2005,36(6)：895-896.
[66]霍塞虎.多巴胺D2受体基因及其多态性与物质依赖的相关研究[J].健康研究,2009,29(3)：214-218.
[67]汪广剑,张理义,仲爱芳等.5-羟色胺2A受体基因多态性与海洛因依赖患者的相关性研究[J].四川精神卫生,2001,14(2)：101-102.
[68]赵敏,杨德森,郝伟等.5-HT2A受体基因102T/C多态性与海洛因依赖易感性的关系[J].中国神经精神疾病杂志,2001,27(3)：224-224.
[69]Reuben M, Clarke PB.Nicotine-evoked [3H]-5-hydroxytryptamine release from rat striatal synaptosomes[J].Neuropharmacology,2000;39:290-299.
[70]Polina ER,Contini V,Hutz MH,et al.The serotonin 2A receptor gene in alcohol dependence and tobacco smoking[J].Drug,Alcohol Depend,2009,101(1-2):128-131.
[71]do Prado-Lima PA, Chatkin JM, Taufer M,et al. Polymorphism of 5HT2A serotonin receptor gene is implicated in smoking addiction [J].Am J Med Genet B Neuropsychiatr Genet,2004,128B (1):90-93.
[72]Haggstram FM, Chatkin JM, Sussenbach-Vaz E,et al.A controlled trial of nortriptyline, sustained-release bupropion and placebo for smoking cessation:preliminary results[J].Pulm Pharmacol Ther. 2006;19(3):205-209.
[73]White MJ,Young RM,Morris CP,et al.Cigarette smoking in young adults:The influence of the HTR2AT102C polymorphism and punishment sensitivity[J].Drug Alcohol Depend,2011,114: 140-146.