摘要
目的：了解新疆和田地区维吾尔族代谢综合征(metabolic syndrome，MetS)的患病情况，测序筛查前列腺六次跨膜蛋白2(six-transmembrane protein of prostate2，STAMP2)基因在新疆和田地区维吾尔族MetS人群中的变异位点，研究STAMP2基因变异与新疆和田地区维吾尔族人MetS的关系，寻找新疆维吾尔族MetS的易感性标记，探讨MetS可能的遗传学机制。方法：对新疆和田地区，年龄≥30岁的维吾尔民族，采取整群随机抽样调研方法，进行流行病学调查研究，共调查了1545例维吾尔族(男性588例，女性957例)；在流行病学调查结果的基础上，依据国际糖尿病联盟（IDF）诊断标准，随机在858例代谢综合征患者中，选取男性女性分别48例共96例的MetS受试者所提取的DNA，对PCR产物采用直接测序的方法对STAMP2基因筛查的，根据连锁不平衡关系和最小等位基因频率(minor allele frequency，MAF)选择常见的代表性变异位点，同时选择功能区的低频率错义突变；(4)应用高通量TaqMan基因分型技术对研究人群进行STAMP2基因tagSNPs的扩增和高通量基因分型，了解代表性变异基因型在维吾尔族人群代谢综合征组和正常对照组中的分布情况，分别探讨STAMP2基因变异与代谢综合征的相关性；(5)数据分析应用SPSSl6.0统计软件包完成，计数资料的关联分析、以及两组或两组以上连续性变量的比较分别采用卡方检验和t检验或ANOVA分析，优势比(odds ratio，OR)和95%可信区间(confidence interval，CI)应用Logistic回归计算得出，使用SNPAlyze7.0遗传分析软件进行遗传代表性Hardy-Weinberg平衡检验以及基因多态位点之间的配对连锁不平衡关系，进而行基因单体型模块判定和选取代表性变异位点，还有构建多态性位点的单体型和相关的统计学分析。结果：(1)对新疆和田地区维吾尔族代谢综合征的流行病学调查结果显示，代谢综合征在新疆和田地区维吾尔族人群中的检出率为55.5%，高血压、中心性肥胖、高血糖及血脂紊乱的检出率分别为47.5%、40.4%、35.9%及31.6%，在40至50岁年龄段最高，女性代谢综合征检出率明显高于男性，影响代谢综合征发生的危险因素可能是性别和饮酒。(2)随机选取96例小样本人群STAMP2基因测序共发现20个变异位点，包括14个新发现的变异位点和6个已知的变异位点，其中包括2个错义突变。计算各位点间连锁不平衡系数，挑选出5个标签SNPs，包括224A/G(rsl981529，Gly75Asp)、364G/A(rs34741656，Alal22Thr)、7414G/A(rs8122)和6031T/G及-237a/c。(3)5个SNPs中6031T/G位点分型失败，-237a/c变异位点在1110例个体中成功基因分型1044例(MAF<5%)，发现突变杂合型25例，未发现突变纯合型。-237a/c变异位点在维吾尔族人MetS病例组和对照组均有分布，其余3个SNPs在新疆和田地区维吾尔族人行人群关联研究。与MetS关联分析显示：在additive遗传模型下rs8122(P=0.032)和rs1981529(P=0.011)变异位点与维吾尔族女性MetS表型明显关联；多元线性回归分析校正年龄、是否患病影响后，在MetS病例组和合计组的血清高密度脂蛋白(High Density Lipoprotein cholesteroal,HDL-c)水平与rs8122(病例组P=0.001，合计组P=0.004)、rsl981529(病例组P=0.024，合计组P=0.009)变异位点明显相关，并且rs8122变异的A等位基因(保护性等位基因)携带者和rsl981529变异的G等位基因(保护性等位基因)携带者HDL-C水平有逐渐减小趋势；单倍型分析发现，女性MetS病例组单倍型l(rs8122-rsl981529-rs34741656，G-A-G)的频率明显高于对照组(Permutation P=0.044)、单倍型2(rs8122-rsl981529-rs34741656，A-G-G)的频率明显低于对照组(Permutation P=0.009)。结论：新疆和田地区维吾尔族人代谢综合征及其各组分检出率较高，特别是40～50岁年龄人群，且女性高于男性。STAMP2基因rs8122和rs1981529位点可能与女性代谢综合征相关，rs8122变异AA基因型和rsl981529变异的GG基因型可能是防止维吾尔女性患有代谢综合征的保护性因素。
Objective: To investigate the prevalence of Metabolic syndrome (MetS) in Uygur.Systematically screen for and examine SNPs of six-transmembrane protein of prostate2(STAMP2) in Uygur ethnic groups and the pattern of intragenic linkage disequilibriumand the haplotype structure were estimated. Then explore the relation between variation ofSTAMP2polymorphisms and MetS in a large cohort from general Uygur population. Weaim to demonstrate effect of candidate genes in MetS pathogenesis from geneticperspectives and further investigate the mechanisms in more polulations.Methods:Subjects were selected from the cross-sectional study of obesity, hypertension,diabetes mellitus, dyslipidemia among Uygur1545individuaIs with aged30-70years inHETIAN area of Xinjiang (male588and female957) based on the epidemiology. Basedon the criteria of international diabetes federation (IDF), there were858MetS subjects.The sequences of the putative promoter region, exon-intron boundaries，and all exons,including the5'-and3'-untranslated regions(UTRs)(～lkb) of STAMP2gene were PCRamplified and sequenced in96Uygur MetS subjects (including48males and48females).Representative variations were selected with linkage disequilibrium (a r2cutoff of0.8),minor allele frequency of>5%and possible function (missense mutation) were genotypedwith TaqMan-PCR method in all subjects，and then constructed a case-control study.Statistical analyses were performed using SPSS version16.0software package. Betweencase and control groups, distributions of patient characteristics, allele and genotypesfrequency of each SNPs were analyzed using the t-test or Chi-square test. Adjusted Oddsratios(ORs) with95%confidence intervals from logistic regression analysis was used toestimate the relative risk of MetS associated with genotype: linkage disequilibrium (LD)analysis was carried out in a pair-wise fashion, the determination of haplotype block andthe estimation and comparation of haplotypes frequencies in two groups were inferred bythe SNPalyzer7.0Pro package. Results：(1)Epidemiology survey result indicated that the prevalence of MetS was55.5%from HeTian Area of Xinjiang in Uygur population.Respectively, prevalence of hypertension, abdominal obesity, hyperglycemia, and bloodlipid disorders were47.5%,40.4%,35.9%and31.6%. The detection rate was highest in40-50years and in female was more than in male. Gender and drinking were the majorrisk factor of MetS.(2)We identified20variations，including14novel variations and6known variations (including2nonsynonymous SNPs) of the STAMP2gene by sequencingin96Uygur patients with MetS. Accounting of linkage disequilibrium relationships andfunctions, five representative variations:224A/G(rsl981529, Gly75Asp),364G/A(rs34741656, Alal22Thr),7414G/A(rs8122),-237a/c and6031T/G (unsuccessfullygenotyped) were genotyped in a large cohort from epidemiological study.(3)The variation-237a/c with MAF<5％was genotyped in1110subjects and found25individuals with acgenotype and found no individuals with CC genotype. The variation-237a/c wasdistributed in the cases and controls of MetS, and was not special for the prevalence ofMetS and its related phenotypes. Of the other3common variations, rs8122(Padditive=0.032)and rsl981529(Padditive=0.011) were significantly associated with MetS phenotype inUygur female populations．By the multiple linear regression analysis controlling age anddisease status confound factors, the significant association of the variations rs8122andrs1981529with HDL-C level in IDF defined-MetS cases (P=0.001,0.024, respectively)and in a combined sample (case+control)(P=0.004，0.009, respectively) were revealed,and the mean values of HDL-C level were gradual decline among A (protection) allelecarriers of rs8122and among G (protection) allele carriers of rs1981529in both MetScases and the combined sample．The association between haplotypes of the STAMP2genepolymorphisms and MetS was further performed. Haplotype (G-A-G)(rs8122-rsl981529-rs34741656) were associated with a higher prevalence of MetS(Permutation P=0.044) and haplotype (A-G-G)(rs8122-rsl981529-rs34741656) wasassociated with a lower prevalence of MetS (Permutation P=0.009) in Uygur female.
Conclusion：The prevalence of MetS and and its components were higher in XinjiangUygur population. The detection rate was highest among age40to50, and the prevalenceof MetS in male Uygur population was significantly lower than in female. STAMP2genetic variations are likely to be associated with metabolic syndrome of female Uygur.
引文
[1]赵冬,郑峥.代谢综合征(1)代谢综合征的研究进展(续前)[J].中国循环杂志,2011,26(2):87-88.
[2] Hunt K. National Cholesterol Education Program versus World HealthOrganization metabolic syndrome in relation to all-cause and cardiovascularmortality in the San Antonio Heart Study [J]. Circulation,2004,110:1245-1251.
[3] Najarian RM, Sullivan LM, Kannel WB，et al.Metabolic syndrome compared withtype2diabetes mellitus as a risk factor for stroke：The framingham offspring study[J]. Arch Intern Med,2006,166(1):106-11.
[4] Bo I, Peter A, Tiinamaija T, et al. Cardiovascular morbidity and mortalityassociated with the metabolic syndrome [J]. Diabetes Care,2001,24:683-686.
[5] YangW, Reynold K, Gu D, et al. A comparison of two proposed definitions formetabolic syndrome in the Chinese adult population [J]. AJM,2007,334(2):184-189.
[6]李岩,赵冬,王薇,等.中国11省市3564岁人群应用不同代谢综合征诊断标准的比较[J].中华流行病学杂志，2007,28(1):83-87.
[7] Lin JW, Caffrey JL, Chang MH, Lin YS. Sex, menopause, metabolic syndrome,and all-cause and cause-specificmortality--cohort analysis from the Third NationalHealth and NutritionExamination Survey [J]. J Clin Endocrinol Metab.2010.95(9):4258-67.
[8] Ford ES, Giles WH, Dieta WH. Prevalence of the metabolic syndrome among USadult: findings form the third National Health and Nutrition Examination Survey[J]. JAMA,2002,287:356-360.
[9] Ozsahin AK, Gokeel A, Sezgin N, et al. Prevalence of the metabolic syndrome in aTurkish adult pupulation[J]. Diabetes Nutr Metab,2004,17:230.
[10] JanssenI, Powel LH, Crawford S, et al. Menopause and the Metabolic Syndrome:The Study of Women′s Health Across the Nation [J]. Arch Intern Med,2008,168(14):1568-1575.
[11] Jie WP, Xinjiang KS, Chen L, et al. Epide miologic study on metabolic syndromein normal and overweight Chinese in Shanghai [J]. Diabetes,2008,49(suppl):48-52.
[12] Jia WP, Xiang KS, Chen L, et al. Acomparison of the application of two workingdeinition of metabolic syndrome in Chines population [J]. Zhonghua Yi Xue Za Zhi,2004,84:534-538.
[13] Reaven GM. Banting Lecture1988：role of insulin resistance in human disease[J].Diabetes,1988,37:1595-1607.
[14] ReavenGM. Role of insulin resistance in human disease [J]. Diabetes,1988:37:1595-1607.
[15] Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetesmellitus and its complications. Partl: diagnosis and classification of diabetesmellitus provisional report of a WHO consultation[J]. Diabet Med.1998,1(7):539-553.
[16] The European Group for the Study of Insulin Resistance (EGIR). Frequency of theWHO metabolic syndrome in European cohorts, and an alternative definition of aninsulin resistance syndrome [J]. Diabetes Metab.2002,2:354-376.
[17] Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol inAdults. Executive Summary of The Third Report of The National CholesterolEducation Program (NCEP) Expert Panel on Detection, Evaluation, And Treatmentof High Blood Cholesterol In Adults(Adult Treatment Panel III)[J]. JAMA.2001，285:2486-2497.
[18] Einhorn position D, Reaven GM, statement on the Cobin RH, et al. AmericanCollege of Endocrinology insulin resistance syndrome [J]. Endocr Pract.2003,9:237-252.
[19]中华医学会糖尿病学分会代谢综合征研究协作组.中华医学会糖尿病学分会关于代谢综合征的建议[J].中华糖尿病杂志,2004,12(3):156-161.
[20] International Diabetes Federation (IDF). The IDF consensus worldwide definitionof the metabolic syndrome [DB/OL].[2005-04-28]http://www. idforg/webdata/ocs/IDF-Meta-syndrome-definition. pdf.
[21]熊英环,南美兰,方今女.延边农村居民代谢综合征不同诊断标准评价[[J].中国公共卫生，2010,26:933-934.
[22]梁国威,王新华,徐旭,等.代谢综合征的不同诊断标准在北京某集团公司工作人员中的应用比较[[J].中国现代医药杂志，2008,10:28-32.
[23]邵继红,金英良,俞黎黎，等.三种代谢综合征诊断标准的应用及评价[J].中国糖尿病杂志.2009,11:801-803.
[24]周北凡,武阳丰,李莹,等.中国成人代谢综合征腰围切点的研究[J].中华心血管病杂志.2005,33:81-85.
[25]张刚,祝之明,赵志钢,等.代谢综合征诊断标准临床应用的比较[J].中华医学杂志.2005,85(7):490-491.
[26] Gu Df, Reynolds K, Wu XG, et al. Prevalence of the metabolic syndrome andoverweight among adults in China [J]. Lancet,2005,365:1398-1405.
[27] Athyros VG, Ganotakis ES, Elisaf M, et al. The prevalence of the metabolicsyndrome using the National Cholesterol Educational Program and InternationalDiabetes Federation definitions [J]. Curr Med Res Opin.2005,21:1157-1159.
[28] Rutter MK, Meigs JB, Sullivan LM, et al. Insulin resistance, the metabolicsyndrome, and incident cardiovascular events in the Framingham OffspringStudy[J]. Diabetes.2005,54:3252-3257.
[29] Kurl S, Laukkanen JA, Niskanen L, et al. Metabolic syndrome and the risk ofstroke in middle-aged men [J]. Stroke.2006,37:806-811.
[30] Taylor H, Liu JK, Wilson q, et al, Distinct Component Profiles and High RiskAmong African Americans With Metabolic Syndrome: The Jackson Heart Study[J].Diabetes Care,2008,31:1248-1253.
[31] Ni RM, Mo YQ, Chen Xl, et al. Low prevalence of the metabolic syndrome buthigh occurrence of various metabolic disorders in Chinese women with polycysticovary syndrome [J]. Eur J Endocrinol,2009,161:411-418.
[32] Edwards KL., Hutter CM.,Wan JY., et al. Genome-wide linkage scan for themetabolic syndrome：the GENNID Study [J].Obesity2008;16：1596-1601．
[33] Gotoda T. Genetic susceptibility to metabolic syndrome [J]. Nippon Rinsho,2004,62(6):1037-1044.
[34] Karen L, Edwards, Huttercm.，Wan JY, et al. Genome-wide Linkage Scan for theMetabolic Syndrome: The GENNID Study [J]. Obesity,2008,16,1596-160.
[35] Argyropoulos G, Smith S, Bouchard C. Genetics of the metabolic syndrome InInsulin Resistance [M]. West Essex England,2005, pp401-450.
[36] Chakravarti A, Little P. Nature, nurture, and human disease [J]. Nature.2003,421:412-414.
[37] Guttmacher AE, Collins FS, Carmona. The family history-more important thanever [J]. N Eng J Med.2004,351:2333-2336.
[38] Teran-Garcia M, Bouchard C. Genetics of the metabolic syndrome [J]. ApplPhysiol Nutr Metab.2007,32:89-114.
[39] Yah W, YangX, Zheng Y,et al. The metabolic syndrome in Uygmc and Kazakpopulations[J].Diabetes Care.2005,28:2554-2555.
[40]郭艳英,王坤,赵蕾,等.新疆博尔塔拉州维、哈、蒙、汉四民族代谢综合征的流行病学调查[J].中华内科杂志2006,45:227-228.
[41]潘长玉,程莹.代谢综合征：值得关注的心血管疾病高危因素[J].中华内科杂志,2004,43:801-802.
[42]顾东风, Reynolds K,杨文杰,等.中国成年人代谢综合征的患病率[J].中华糖尿病杂志,2005,13:181-186.
[43]陈蕾,贾伟平,陆俊茜,等.上海市成人代谢综合征流行病学调查[J].中华心血管病杂志,2003,31:909-912.
[44]脑卒中、冠心病发病危险因素进一步研究协作组11省市队列人群代谢综合征的流行病学调查[J].中华预防医学杂志,2002,36:298-300.
[45] Gu D, Reynolds K, Wu X, et al. Prevalence of the metabolic syndrome andoverweight among adults in China [J]. Lancet.2005,365:1398-1405.
[46] Wellen KE, Hotamisligil G.S. inflammation，stress，and diabetes [J]. J Clin. Invest.2005.115:1111-1119.
[47] Hotmnisligil G.S. Inflammation and metabolic disorders [J]. Nature,2006,444:860-867.
[48] Qatanani M., Lazar MA. Mechanisms of obesity-associated insulin resistance:many choices on the menu [J]. GENE&DEVELOPMENT2008,21:1443-1455.
[49] Tilg H, Moschen AR. Inflammatory mechanisms in the regulation of insulinresistance [J]. MOLMED,2008,14:222-231.
[50] Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression oftumornecrosis factor-alpha: director role in obesity-linked insulin resistance[J]. Science1993,259:87-91.
[51] Hotamisligil GS，Ariler P， Caro JF，et a1．Increased adipose tissue expression oftumor necrosis factor-alpha in human obesity and insulin resistance [J].J ClinInvest,1995,95:2409-2415.
[52] Shoelson SE.，Lee J， C0ldfine AB．Inflammation and insulin resistance [J]. J ClinInvest,2006,116:1793-1801．
[53] Wellan KE, Hotamisligil GS．Inflammation, stress，and diabetes[J]. J Clin Invest，2005,115：1111-1119.
[54] Weisberg SP, McCam D, Desai M, et a1．Obesity is associated with macrophageaccumulation in adipose tissue [J]. J Clin Invest,2003,112:1796-1808.
[55] Xu H, Barnes GT，Yang Q, et al. Chronic inflammation in fat plays a emcialrole inthe development of obesiky-related insulin resistance [J]. J ClinInvest,2003,112:1821-1830.
[56] NeeIs JG, Olefsky JM. Inflamed fat: what starts the fire?[J].J Clin Invest,2006,116:33-35.
[57] Shi H3, Kokoeva MY, Inouve K, et a1.TLR4links innate immunity and fattyacid-induced insulin resistance [J]. J Clin Invest,2006,116:3015-3025.
[58] Ritchie SA, Connell JM. The link between abdominal obesity, metabolic syndromeand cardiovascular disease[J].Nutr Metab Cardiovase Dis.2007,17:319-326.
[59] Moldes M, Lasnier F, Gauthereau X., et a1. Tumor necrosis factor-alpha-inducedadipose-related protein(TIARP), a cell surface protein that is highly induced bytumor necrosis factor-alpha and adipose conversion[J].J Biol Chem.2001,276,33939-33946.
[60] Fasshauer M, Kralisch S, Klier M, et a1.Interleukin-6is a positive regulator oftumor necrosis factor a-induced adipose-related protein in3T3-L1adipocytes [J].FEBS Lett.2004,560,153-157.
[61] Kralisch S., Sommer G., Weise S., et a1．Interleukin-lβ is a positive regulator ofTIARP/STAMP2gene and protein expression in asipocytes in vitro [J]. FEBS Lett2009,583:1196-1200.
[62] Fasshauer M., Klein J., Krahlisch S., et a1. GH is a positive regulator of tumornecrosis factor a-induced adipose related protein in3T3-L1adipocytes[J]. JEndocrinol2003,178:523-53l.
[63] Wellen，K．E., Fucho，R．，Gregor，M．F.er a1．Coordinated ReguIation ofNutrientand Inflarmmatory Responses by STAMP2Is Essential for Metabolic Homeostasis[J]. J Cell．2007，129，537-548.
[64] Ramadoss P, Chiappini F, Bilbam M., et al. Regulation ofhepatic sixtransmembrance epithelial antigen of prostate4(STEAP4) expression by STAT3and C/EBPa[J]. J Biol Chem．2010.285:16453-16466.
[65] Arner P., Stenson BM., Dungner E，et al. Expression of STEAP4in human adiposetissue associates Wjth adiposity and insulin resistance [J].J Clin Endocrin Metab.,2008,93:2249-2254.
[66] Zhang CM, Chi X, Wang B, et a1. Downregulation of STEAP4, a highly-expressedTNF-a-inducible gene in adipose tissue.is associated with obesity in human[J].ActaPharmacol Sin,2008,29:587-592.
[67] Chen X, Zhu C, Ji C,et a1.STEAP4,a gene associated with insulin sensitivity,isregulated by several adipokines in human adipocytes[J].Int J Mol Med.2010,25:361-367.
[68] Laramie JM, Wilk JB, Williamson SL, et a1.Multiple Genes Influence BMI OnChromosome7q31-34： TheNHLBIFamilyHeart Study [J]. Obesity2009;17:2182-2189.
[69] Hanson RL, Ehm MG,Pettitt DJ, et al. An autosomal genomic scan for loci linkedto type II diabetes mellitus and body-mass index in Pima Indians [J]. Am J HumGenet1998;63:1130-1138.
[70] Cheng LS,Davis RC.Raffel LJ,et a1．Coincident linkage of fasting plasma insulinand blood pressure to chromosome7q in hypertensive Hispanic families [J].Circulation2001;104:1255-1260.
[71] An P, Freedman BI, Hanis CL, et a1.Oenome-wide linkage scans for fastingglucose，insulin，and insulin resistance in the national heart，lung，and bioodinstitute family blood pressure program：evidence of linkages t6chromosome7q36and19q13from meta-analysis[J].Diabetes2005;54:909-914.
[72] Khokhar KK, Sidhu S, and Kaur G Correlation between leptin level andhypertension in normal and obese pre-and postmenopausal women[J]. Eur JEndocrinol,2010,163:873-878.
[73] Smith SM and Mayer-Davis EJ. Leptin in Relation to Hypertension:The Role ofObesity in the Insulin Resistance Atherosclerosis Study(IRAS)[C]. Circ MeetingAbstracts,2001;103:1361-1365.
[74] Voelker R. Leptin Link to Hypertension [J]. JAMA,1999;282:1322-1327.
[75] Sonmez A, Kisa U, Uckaya G, et al. Effects of losartan treatment on T cell activitiesand plasma leptin concentrations in primary hypertension [J]. Journal ofRenin-Angiotensin-Aldosterone System,2001,2:112-116.
[76] Gannage-Yared MH, Khalife S, Semaan M, et al. Serum adiponectin and leptinlevels in relation to the metabolic syndrome, androgenic profile and somatotropicaxis in healthy non-diabetic elderly men[J]. Eur J Endocrinol,2006,155:167-176.
[77] Xydakis AM, Case CC, Jones PH, et al. Adiponectin, Inflammation and theExpression of the Metabolic Syndrome in Obese Individuals: The Impact of RapidWeight Loss through Caloric Restriction [J]. J Clin. Endocrinol Meta,2004,89:2697-2703.
[78] Meija Santaniemi, Y Antero adiponectin Endocrinol.concentration is an Kesaniemi,and Olavi Ukkola. Low plasma indicator of the metabolic syndrome [J]. Eur. J.Nov2006;155:745-750.
[79] Yasuharu Tabara, Haruhiko Osawa, Ryuichi Kawamoto, et al. ReducedHigh-Molecular-Weight Adiponectin and Elevated High-Sensitivity C-ReactiveProtein Are Synergistic Risk Factors for Metabolic Syndrome in a Large-ScaleMiddle-Aged to Elderly Populationahe Shimanami Health Promoting ProgramStudy [J]. J. Clin. Endocrinol. Metab, Mar2008;93:715-722.
[80] Fu-Mei Chung, Dao-Ming Chang, Miao-Pei Chen, et al. Areca Nut Chewing IsAssociated with Metabolic Syndrome:Role of tumor necrosis factor-a, leptin, andwhite blood cell count in betel nut chewing-related metabolic derangements[J].Diabetes Care,2006,29:1714.
[81] Picchi A, Gao X, Belmadani S, et al. Tumor Necrosis Factor-a induces EndothelialDysfunction in the prediabetic Metabolic Syndrome [J]. Circ Res,2006,99:69-77.
[82] Lo J, Bemstein LE, Canavan B, et al. Effects of TNF-a neutralization onadipocytokines and skeletal muscle adiposity in the metabolic syndrome [J]. Am JPhysiol Endocrinol Metab,2007,293: E102-E109.
[83] Banks WA, Willoughby LM, Thomas DR,et al. Insulin Resistance Syndrome in theE1derly: Assessment of functional, biochemical, metabolic and inflammatory status[J]. Diabetes Care,2007,30:2369-2373.
[84] Yang C, Badeanlou L, Bielawski J, et al. Central role of ceramide biosynthesis inbody weight regulation, energy metabolism, and the metabolic syndrome [J]. AmPhysiol Endocrinol Metab,2009,297:E211-E224.
[85] Burgess A, Li M, Vanella L, et al. Adipocyte Heme Oxygenase-1InductionAttenuates Metabolic Syndrome in Both Male and Female Obese Mice[J].Hypertension,2010,56:1124-1130.
[86] Spurlock ME and Gabler NK. The Development of Porcine Models of Obesity andthe Metabolic Syndrome [J]. J Nutr,2008,138:397-402.
[87] Qi QB, Wang J, Li HX, et al. Associations of resistin with inflammatory andfibrinolytic markers, insulin resistance, and metabolic syndrome in middle-agedand older Chinese [J]. Eur J Endocrinol,2008,159:585-593.
[88] Norata GD, Ongari M, Garlaschelli K, et al. Plasma resistin levels correlate withdeterminants of the metabolic syndrome [J]. Eur J Endocrinol,2007,156:279-284.
[89] Vadacce M, Margiottad, Rigon A, et al. Adipokines and Systemic LupusErythematosus:Relationship with Metabolic Syndrome and Cardiovascular DiseaseRisk Factors[J]. J Rheumatol,2009,36:295-297.
[90] Szapary PO, Bloedon LT, Samaha FF, et al. Effects of Pioglitazone on Lipoproteins,Inflammatory Markers, and Adipokines in Nondiabetic Patients with MetabolicSyndrome [J]. Arterioscler Thromb Vasc Biol,2006,26:182-188.
[91] Banks WA, Willoughby LM, Thomas DR, et al. Insulin Resistance Syndrome in theElderly: Assessment of functional, biochemical, metabolic, and inflammatory status[J]. Diabetes Care,2007,30:2369-2373.
[92] ManolioTA，BrooksLD，andCollins FS．A HapMap harvest of insights into thegenetics of common disease [J]. J Clin Invest2008;118:1590-1605.
[93]方福德.我国2型糖尿病遗传研究向何处去?[J].中国糖尿病杂志,2008,16:577-579.
[94] Ng SB, Turner EH, Robertson PD, et a1. Targeted capture and massively parallelsequencing of l2human exons [J]. Nature,2009,461:272-276．
[95] Li NF, Wang HM, Yang J, et a1. Serum uric acid is associated with metabolic riskfactors for cardiovascular disease in the Uygur population [J]. Physiol Nutr Metab,2009,34:1032-1039．
[96] Yao XG, Fromlet F, Zhou L, et a1. The prevalence of hypertension，obesity anddyslipidemia in individuals of over30years of age belonging to minorities fromthe pasture area of Xinjiang[J]. BMC Public Health2010,10:91-98.
[97]王红梅,李南方,姚晓光,等.新疆阜康牧区哈萨克族人群高血压的群体流行病学研究[J].中华高血压杂志2010,10-14.
[98]李南方,陶沙,张德莲,等.新疆牧区哈萨克族与蒙古族低密度脂蛋白胆固醇水平调查与影响因素分析[J].中华心血管病杂志2008,36:1125-1127．
[99]周玲,李南方,张德连,.等.新疆牧区哈、蒙两民族血脂水平调查[J].中国康复医学杂志,2004,19:211-213.
[100]陶沙,李南方,周玲,等.新疆牧区哈萨克族与蒙古族女性非高密度脂蛋白胆固醇水平调查与分析[J].新疆医学,2009,39:19-21.
[101]陶沙,洪静,周玲,李南方,等.新疆牧区哈萨克族与蒙古族老年人非高密度脂蛋白胆固醇水平调查与分析[J].新疆医学,2008,38:40-42.
[102]李南方,周玲,曹梅等.新疆和丰县牧区高血压病流行病学调查报告现代预防医学2003,30:141-143.
[103]周玲,李南方.新疆牧民超重和肥胖的现况调查[J].实用预防医学,2003,10：884-885.
[104]周玲,李南方,殷晓娟等.新疆牧区少数民族血脂水平调查现代预防医学2003,30:529-531.
[105]李南方,周玲,曹梅,等.新疆和丰县牧区高血压流行现状及其相关因素分析[J].心血管康复医学杂志,2002,11:201-203.
[106] Zabetian A, Hadaegh F, Azizi F. Prevalence of metabolic syndrome in Iranian adultpopulation, concordance between the IDF with the ATPIII and the WHOdefinitions[J]. Diabetes Res Clin Pract.2007,77(2):251-257.
[107] Deepa M, Farooq S, Datta M, et al.Prevalence of metabolic syndrome using WHO,ATPIII and IDF definitions in Asian Indiansahe chennai urban rural epidemiologystudy(CURES-34)[J]. Diabetes Metab Res Rev.2007,23(2):127-134.
[108] Cameron AJ, Magliano DJ, Zimmet PZ, et al. The metabolic syndrome in Australia:prevalence using four definitions [J]. Diabetes Res Clin Pract.2007,77(3):471-478.
[109] Choi KM, Kim SM, Kim YE, et al. Prevalence and cardiovascular disease risk ofthe metabolic syndrome using national cholesterol education program andinternational diabetes federation definitions in the Korean population [J].Metabolism.2007,56(4):552-558.
[110] Csaszar A, Kekes E, Abel T, et al. Prevalence of metabolic syndrome estimated byinternational diabetes federation criteria in a Hungarian population[J]. BloodPressure.2006,15(2):101-106.
[111]李秀均.代谢综合征[M].第2版.北京:人民卫生出版社,2007:102-30.
[112] Bjorge T, Lukanova A, Jonsson H, et al. Metabolic Syndrome and Breast Cancer inthe Me-Can (Metabolic Syndrome and Cancer) Project [J]. Cancer Epidemiol.Biomarkers Prev.2010;19:1737-1745.
[113] Johansen D, Stocks T, Jonsson H, et al. Metabolic Factors and the Risk ofPancreatic Cancer:A Prospective Analysis of almost580,000Men and Women inthe Metabolic Syndrome and Cancer Project[J]. Cancer Epidemiol. BiomarkersPrev,2010;19:2307-2317.
[114] Raffaitin C, Feart C, Goffml, et al. Metabolic syndrome and cognitive decline inFrench elders: The Three-City Study[J]. Neurology,2011,76:518-525
[115] Nagel G，Concin H, Bjorge T, et al. Metabolic syndrome and rare gynecologicalcancers in the Metabolic syndrome and Cancer project (Me-Can)[J]. Ann. Onc，2010,10(1093):597.
[116] Cheung BMY, Wat NMW, Man YB, et al. Development of diabetes in Chinese withthe metabolic syndrome-a six year prospective study [J]. Diabetes Care,2007,30(6):1430-1436.
[117] Rosato V, Zucchetto A, Bosetti C, et al. Metabolic syndrome and endometrialcancer risk [J]. Ann. Onc,2010,10(1093):464-466.
[118] Marchesini G and Bianchi G Metabolic syndrome: relevant for all types of chronicliver diseases?[J]. Gut,2010,59:1314-1315.
[119] Barge T, Stocks T, Lukanova A, et al. Metabolic Syndrome and EndometrialCarcinoma [J]. Am. J. Epidemiol,2010,171:892-902.
[120] Solfrizzi V, Scafato E, Capurso C, at al. Metabolic syndrome and the risk ofvascular dementiaahe Italian Longitudinal Study on Ageing [J]. J.Neurol.Neurosurg. Psychiatry,2010,81:433-440.
[121] Iso H, Sato S, Kitamura A, et al. Metabolic Syndrome and the Risk of IschemicHeart Disease and Stroke among Japanese Men and Women [J]. Stroke,2007,38:1744-1751.
[122] McNeill AM, Rosamond WD, Girman CJ, et al. The Metabolic Syndrome and11-Year Risk of Incident Cardiovascular Disease in the Atherosclerosis Risk inCommunities Study [J]. Diabetes Care,2005,28:385-390.
[123] Watanabe H, Tanabe N, Watanabe T, et al. Metabolic Syndrome and Risk ofDevelopment of Atrial Fibrillation:The Niigata Preventive Medicine Study[J].Circulation,2008,117:1255-1260
[124] Dentali F, Romualdi E and Ageno W. The metabolic syndrome and the risk ofthrombosis [J]. Haematologica,2007,92:297-299.
[125] Chen HJ, Bai CH, Yeh WT, et al. Influence of Metabolic Syndrome and GeneralObesity on the risk of Ischemic Stroke [J]. Stroke,2006,37:1060-1064.
[126] Kurl S, Laukkanen JA, Niskanen L, et al. Metabolic Syndrome and the Risk ofStroke in Middle-Aged Men [J]. Stroke,2006,37:806-811.
[127] Yaffe K, Kanaya A, Lindquist K, et al. The Metabolic Syndrome, Inflammation,and Risk of Cognitive Decline [J]. JAMA,2004,292:2237-2242
[128] Laukkanen JA, Laaksonen DE, Niskanen L, et al. Metabolic Syndrome and theRisk of Prostate Cancer in Finnish Men: A Population-Based Study [J]. CancerEpidemiol. Biomarkers Prev,2004,13:1646-1650.
[129] Olson JM, Wijsman EM. Design and sample-size considerations in the detection oflinkage disequilibrium with a disease locus. Am J Hum Genet,1994;55:574-580.
[130]中国肥胖问题工作组.中国成人超重与肥胖症预防与控制指南[J].营养学报,2004,26(1)1-4.
[131]中国高血压防治指南修订委员会.2005年中国高血压防治指南[J].中华心血管病杂志,2005,32(12)1060-1064.
[132]《中国成人血脂异常防治指南》制订联合委员会.中国成人血脂异常防治指南
[M].北京:人民卫生出版社,2007: pp.16-17.
[133]黄金,秦玉菊,周卫东,等.长沙市4083名成人代谢综合征患病状况调查及危险因素分析[J].中国现代医学杂志.2008,18(23):3509-3513.
[134]卢伟,刘美霞,李锐,等.上海15～74岁居民代谢综合征的流行特征[J].中华预防医学杂志.2006,40(4):262-267.
[135]王贵新,张书杰,韩波.沈阳部分职业人群代谢综合征调查分析[J].中国现代医学杂志.2006,16(19):2971-2973.
[136]赵凤丛,葛家璞,张洁,等.新疆20-74岁居民代谢综合征流行病学调查[J].新疆医科大学学报.2009,6:57-60.
[137]胡尔西达,曾小云,谢自敬,等.乌鲁木齐市汉族人群代谢综合征流行病学基线调查[J].中国临床康复.2004,8(27):5850-5851.
[138]安娜,朱药,尹琦,等.乌鲁木齐市水磨沟区居民代谢综合征患病率的调查[[J].中国慢性病预防与控制，2009,2:172-173.
[139]张洁,葛家璞,伊万,等.吐鲁番地区维吾尔族空腹血糖(FBG)≥5.6mmol/L者代综合征(MS)患病情况[J].新疆医学.2008,38:29-31.
[140] Yan W, Yang X, Zheng Y, et al. The metabolic syndrome in Uygur and Kazakpopulations. Diabetes Care.2005,28:2554-2555.
[141] Corry DB. Se-related differences in the insulin resistance syndrome. CurrHypertens Rep.2001,3:(2):124-128.
[142]胡才友,黄慧,杨泽,等.成人代谢综合征的不同组分与其发病的关系[J].中国临床保健杂志.2006,9(1):17-20.
[143] HamsenBC.ThemetaboliesyndromeX[J].AnllNYAcadSei，1999，892:1224.
[144] Lowell BB. Susulic V, Hamann A, et al. Development of obesity in transgenic miceafter genetic ablation of brown adipose tissue[J].Nature,1993,366,740-742.
[145] Recasens M, Rican W, Fernandez-Real3M. Obesity and inflammation[J]. RevistaDe Medicina De La Universidad De Navarra,2004,48(2):49-52.
[146] Monteiro R, Azevedo I Chronic inflammation in obesity and the metabolicsyndrome. Mediators Inflamm [J].2010. pii:289645. Epub2010Jul14.
[147] Viutanen KA, Lidell ME, orava J, et al. Functional brown adipose tissue in healthyadults. N Engl J Med,2009,360:1518-1525.
[148] Cypess AM, Lehrnan S, Williams G, et al. Identification and importance of brownadipose tissue in adult humans [J]. N Engl J Med.2009,360:1509-1517.
[149] Butler AA, Kesterson RA, Khong K, Cullen MJ, A unique metabolic syndromecauses obesity in the melanocortin-3receptor-deficient mouse [J]. Endocrinology.2000,141(9):3518-21.
[150] Nisoli E, Carruba MO. Emerging aspects of pharmacotherapy for obesity andmetabolic syndrome [J]. Pharmacol Res.2004,50(5):453-469.
[151] Fernandez Twinn DS, Ozanne SE. Mechanisms by which poor early growthprograms type-2diabetes, obesity and the metabolic syndrome [J]. Physiol Behav.2006,88(3):234-243.
[152] Edwards KL., Hutter CM.,Wan JY., et al. Genome-wide linkage scan for themetabolic syndrome：the GENNID Study[J]. Obesity2008;16：1596-1601．
[153] Edwards KL, Hutter CM, W, an JY, et al. Genome-wide linkage scan for themetabolic syndrome: the GENNID study[J]. Obesiy,2008,16:1596-1601.
[154] Ohgami RS, Campagna DR, McDonald A, et a1. The Steap proteins aremetalloreductases[J]. Blood,2006,108(4):1388-1394.
[155] Hironori Waki, Peter Tontonoz, STAMPing out Inflammation, Cell,2007,129(4):451-452.
[156] Fasshauer, M, Kralisch, S, Klier, M, et al. Interleukin-6is a positive regulator oftumor necrosis factor alpha-induced adipose-related protein in3T3-L1adipocytes[J]. FEBS LETTERS,2004,560(3)153-157.
[157] Miot A, Maimaitiming S, Emery N, et al.. Genetic variability at the sixtransmembrane protein of prostate2locus and the metabolic syndrome: the datafrom an epidemiological study on the Insulin Resistance Syndrome (DESIR) study[J]. J Clin Endocrinol Metab.2010.95(6):2942-7.
[158]汪维鹏,倪坤仪,周国华.单核苷酸多态性检测方法的研究进展[J].遗传,2006,28(1):117-126.
[159] International HapMap Consortium. A second generation human haplotype map ofover3.1million SNPs [J]. Nature.2007,449:851-61.
[160] Manolio TA, Brooks LD, Collins FS. A HapMap harvest of insights into thegenetics of common disease [J]. J. Clin. Invest.2008,118(5):1590–605.
[161] Yao XG, Fromlet F,Zhou L, et a1. The prevalence of hypertension，obesity anddyslipidemia in individuals of over30years of age belonging to minorities fromthe pasture area of Xinjiang[J]. BMC Public Health2010,10:91-98.
[162]王红梅,李南方,姚晓光等．新疆阜康牧区哈萨克族人群高血压的群体流行病学研究[J].中华高血压杂志2010,10.
[163]李南方,陶沙,张德莲等.新疆牧区哈萨克族与蒙古族低密度脂蛋白胆固醇水平调查与影响因素分析[J].中华心血管病杂志2008,36:1125-1127.
[164]周玲,李南方,张德连,等.新疆牧区哈、蒙两民族血脂水平调查[J].中国康复医学杂志,2004,19:211-213.
[165]陶沙,李南方,周玲,等.新疆牧区哈萨克族与蒙古族女性非高密度脂蛋白胆固醇水平调查与分析新疆医学2009,39:19-21．
[166]陶沙,洪静,周玲,李南方,等.新疆牧区哈萨克族与蒙古族老年人非高密度脂蛋白胆固醇水平调查与分析新疆医学2008,38:40-42.
[167]李南方,周玲,曹梅,等新疆和丰县牧区高血压病流行病学调查报告现代预防医学2003,30:141-143.
[168]周玲,李南方.新疆牧民超重和肥胖的现况调查[J].实用预防医学,2003,10:884-885.
[169]周玲,李南方,殷晓娟等.新疆牧区少数民族血脂水平调查[J].现代预防医学2003,30:529-531.
[170]李南方,周玲,曹梅,等新疆和丰县牧区高血压流行现状及其相关因素分析[J].心血管康复医学杂志,2002,11:201-203．
[171] Matthews DR., Hosker JP., Rudenski AS., et aI．Homeostasis model assessment：insulin resistance and beta-cell function from fasting plasma glucose and insulinconcentrations in man [J].Diabetologia1985,28:412-419.
[172] World Health Organization-Western Pacific Region, the international associationfor the study of obesity and the international obesity taskforce[J]. PerspectiveRedefining Obesity and its Treatment.February,2000.
[173]中国成人血脂异常防治指南制订联合委员会.中国成人血脂异常防治指南[J].中华心血管病杂志2007,35:390-409.
[174]中华医学会糖尿病学分会MetS研究协作组.中华医学会糖尿病学分会关于代谢综合征的建议[J].中华糖尿病杂志2004,12:156-161．
[175] LI NF,LUG WL，ZHANG JH et al. Associations of Genetic Variations in theFURIN gene with Hypertension [J]. BMC Medicine Genetics2010,13:124-127.
[176]王红梅,李南方,姚晓光等.神经前体细胞表达发育调控样基因rs4149601多态性与新疆哈萨克族人群中心性肥胖的关联研究[J].中华医学遗传学杂志,20l0,27:668-671.
[177]王红梅,李南方,姚晓光,等. NEDD4L基因rs3865418多态性与哈族高血压病的关联研究[J].临床心血管病杂志,2010,28:614-617.
[178] LI NF, ZHANG JH YANG JJ Association of genetic variations of regulator ofG-protein signaling2with hypertension in the general Xinjiang Kazakh population[J]. Clinical and Experiment Hypertension,2010,35:256-261.
[179]张菊红,严治涛,郭艳英,等. G蛋白信号转导调节蛋白-2基因1891-1892del TC多态性与新疆哈萨克族男性原发性高血压关系[J].中华医学遗传学杂志2010.27(1):29-33.
[180]张菊红,严治涛,姚晓光,等. G蛋白信号转导调节蛋白-2基因外显予在原发性高血压患者中的测序分析.中国医学科学院学报2011,33:200-204.
[181] LI NF, ZHANG JH. CHANG JH．et a1．The association study of genetic variationsof prostasin gene with the essential hypertension in Xinjiang Kazakh population [J].Chinese Medical Journal2011,124(14):2107-12.
[182]郭艳英,李南方,王昌敏,等.新疆维吾尔族人STEAP4基因遗传变异的分布及其与代谢综合征的关系[J].中华医学遗传学杂志,2011,28(1):78-82.
[183] LI NE WANG HM，YANG J．et al，Genetic variatiOn of NEDD4L is associatedwith essential hypertension in female Kazakh general population：a case-controlstudy[J]. BMC MED GENET.2010,1:10-13．
[184]郭艳英,李南方,姚晓光,等. NEDD4基因变异与新疆哈萨克族人高血压的相关性研究[J].中国科学院学报,2009,31(6):679-685．
[185]王红梅,李南方,洪静等．神经前体细胞表达发育调控样蛋白4基因多态性与哈萨克族高血压病的关联研究[J].中华心血管病杂志,2010,26:614-617,
[186] LI NF, GUO YY., WANG HM, et al．Variations of six transmembrane epithelialantigen of prostate4(STEAP4) gene are associated with metabolic syndrome infemale Uygur general popuMdon. Archives of Medical Research2010,41(6):449-56.
[187] Korkmaz, C.G. KorPkmaz, K.S., Kurys, et al.Molecular cloning andcharacterization of STAMP2, an androgen-regulated six transmembrane proteinthat is overexpressed in prostate cancer [J]. Oncogene,2005,24,4934-4945.
[188] Yah W,Gu D., Yang X., et al. High-density lipoprotein cholesterol levels increasewith age，body mass index，blood pressure and Nsting biood glucose in a ratalUygur population in China [J]. J Hypertens2005,23:1985-1989.
[189] Korkmaz, C.G KorPkmaz, K.S., et al．Molecular cloning and characterization ofSTAMP2, an androgen-regulated six transmembrane protein that is overexpressedin prostate cancer [J]. Oncogene2005,24,4934-4945.
[190] Yah W, Gu D., Yang X., et al. High-density lipoprotein cholesterol levels increasewith age，body mass index，blood pressure and Nsting biood glucose in a ratalUygur population in China [J]. Hypertens2005,23:1985-1989．
[191] Wang GJ, Yang P,Xie HG. Gene variants in noncoding regions and their possibleconsequences [J]. Pharmacogenomics2006,7:203-209．
[192] Conklin D, Jonassen I, Aasland R, et a1. Association of nucleofide patterns withgene function classes: application to human3’untranslated sequences[J].Bioinfonnatics,2002,18:182-189.
[193] Ng PC, Levy S,Huang J, et al：Genetic Variation in an Individual Human Exome [J].PLoS Genet.2008,4：e1000160.
[194] Ohgami RS, Campagna DR, McDonald A, et a1. The steap proteins aremetalloreductases [J]. Blood2006,108:1388-1394.
[1] Punjabi NM.The epidemiology of adult obstructive sleep apnea[J].Proc Am ThoracSoc.2008.5(2):136-43.
[2] Phillips CL, Cistulli PA. Obstructive sleep apnea and hypertension: epidemiology,mechanisms and treatment effects[J].Minerva Med.2006.97(4):299-312.
[3] Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive sleep apnea: apopulation health perspective[J].Am J Respir Crit Care Med.2002.165(9):1217-39.
[4] Hudgel DW. Mechanisms of obstructive sleep apnea[J].Chest.1992.101(2):541-9.
[5] Hotamisligil GS. Inflammation and metabolic disorders[J].Nature.2006.444(7121):860-7.
[6] Waki H, Tontonoz P. STAMPing out Inflammation[J]. Cell.2007.129(3):451-2.
[7] Koehler U, Becker HF, Grimm W, Heitmann J, Peter JH, Schafer H. Relationsamong hypoxemia, sleep stage, and bradyarrhythmia during obstructive sleepapnea[J].Am Heart J.2000.139(1Pt1):142-8.
[8] Akashiba T, Akahoshi T, Kawahara S, Majima T, Horie T. Effects of long-termnasal continuous positive airway pressure on C-reactive protein in patients withobstructive sleep apnea syndrome[J].Intern Med.2005.44(8):899-900.
[9] Ryan S, Taylor CT, McNicholas WT. Predictors of elevated nuclearfactor-kappaB-dependent genes in obstructive sleep apnea syndrome[J].Am JRespir Crit Care Med.2006.174(7):824-30.
[10] Bhushan B, Guleria R, Misra A, Luthra K, Vikram NK. TNF-alpha genepolymorphism and TNF-alpha levels in obese Asian Indians with obstructive sleepapnea[J].Respir Med.2009.103(3):386-92.
[11] Steiropoulos P, Kotsianidis I, Nena E, et al. Long-term effect of continuouspositive airway pressure therapy on inflammation markers of patients withobstructive sleep apnea syndrome[J].Sleep.2009.32(4):537-43.
[12] Williams A, Scharf SM. Obstructive sleep apnea, cardiovascular disease, andinflammation--is NF-kappaB the key[J].Sleep Breath.2007.11(2):69-76.
[13] Gozal D, Kheirandish-Gozal L. Cardiovascular morbidity in obstructive sleepapnea: oxidative stress, inflammation, and much more[J].Am J Respir Crit CareMed.2008.177(4):369-75.
[14] Inoue K, Takano H, Yoshikawa T. Interleukin-6, obstructive sleep apnea, andobesity[J]. Chest,2003.124(4):1621-2; author reply1622-3.
[15] Bhushan B, Guleria R, Misra A, Luthra K, Vikram NK. TNF-alpha genepolymorphism and TNF-alpha levels in obese Asian Indians with obstructive sleepapnea[J]. Respir Med.2009.103(3):386-92.
[16] Li NF, Yao XG, Zhu J, et al. Higher levels of plasma TNF-alpha and neuropeptideY in hypertensive patients with obstructive sleep apnea syndrome[J].Clin ExpHypertens.2010.32(1):54-60.
[17] Popko K, Gorska E, Potapinska O, et al. Frequency of distribution of inflammatorycytokines IL-1, IL-6and TNF-alpha gene polymorphism in patients withobstructive sleep apnea[J]. J Physiol Pharmacol.2008.59Suppl6:607-14.
[18] Ryan S, Taylor CT, McNicholas WT. Predictors of elevated nuclearfactor-kappaB-dependent genes in obstructive sleep apnea syndrome[J].Am JRespir Crit Care Med.2006.174(7):824-30.
[19] El-Solh AA, Akinnusi ME, Moitheennazima B, Ayyar L, Relia S. Endothelialfunction in patients with post-CPAP residual sleepiness[J].J Clin Sleep Med.2010.6(3):251-5.
[20] Guasti L, Marino F, Cosentino M, et al. Cytokine production from peripheral bloodmononuclear cells and polymorphonuclear leukocytes in patients studied forsuspected obstructive sleep apnea[J]. Sleep Breath.2011.15(1):3-11.
[21] Steiropoulos P, Kotsianidis I, Nena E, et al. Long-term effect of continuouspositive airway pressure therapy on inflammation markers of patients withobstructive sleep apnea syndrome[J]. Sleep.2009.32(4):537-43.
[22] Arias MA, Garcia-Rio F, Alonso-Fernandez A, et al. CPAP decreases plasma levelsof soluble tumour necrosis factor-alpha receptor1in obstructive sleep apnoea[J].Eur Respir J.2008.32(4):1009-15.
[23] Steiropoulos P, Papanas N, Nena E, et al. Inflammatory markers in middle-agedobese subjects: does obstructive sleep apnea syndrome play a role[J].MediatorsInflamm.2010.2010:675320.
[24] Inancli HM, Enoz M. Obstructive sleep apnea syndrome and upper airwayinflammation[J]. Recent Pat Inflamm Allergy Drug Discov.2010.4(1):54-7.
[25] Popko K, Gorska E, Potapinska O, et al. Frequency of distribution of inflammatorycytokines IL-1, IL-6and TNF-alpha gene polymorphism in patients withobstructive sleep apnea[J]. J Physiol Pharmacol.2008.59Suppl6:607-14.
[26] Burioka N, Miyata M, Fukuoka Y, Endo M, Shimizu E. Day-night variations ofserum interleukin-6in patients with severe obstructive sleep apnea syndromebefore and after continuous positive airway pressure (CPAP)[J].Chronobiol Int.2008.25(5):827-34.
[27] Steiropoulos P, Kotsianidis I, Nena E, et al. Long-term effect of continuouspositive airway pressure therapy on inflammation markers of patients withobstructive sleep apnea syndrome[J].Sleep.2009.32(4):537-43.
[28] Ohga E, Tomita T, Wada H, Yamamoto H, Nagase T, Ouchi Y. Effects ofobstructive sleep apnea on circulating ICAM-1, IL-8, and MCP-1[J]. J ApplPhysiol.2003.94(1):179-84.
[29] Shadan FF, Jalowayski A, Fahrenholz J, Dawson A, Kline L. Differential geneexpression in the T-helper lymphocytes of obstructive sleep apnea patients treatedwith nasal continuous positive airway pressure (nCPAP)[J]. Med Hypotheses.2004.63(4):630-2.
[30] Alzoghaibi MA, Bahammam AS. Lipid peroxides, superoxide dismutase andcirculating IL-8and GCP-2in patients with severe obstructive sleep apnea: a pilotstudy[J].Sleep Breath.2005.9(3):119-26.
[31] Ryan S, McNicholas WT. Predictors of elevated nuclear factor-kappaB-dependentgenes in obstructive sleep apnea syndrome[J]. Am J Respir Crit Care Med.2007.174(7):824-30.
[32] Shiina K, Tomiyama H, Takata Y, et al. Effects of CPAP therapy on thesympathovagal balance and arterial stiffness in obstructive sleep apnea[J].RespirMed.2010.104(6):911-6.
[33] Kaditis AG, Ioannou MG, Chaidas K, et al. Cysteinyl leukotriene receptors areexpressed by tonsillar T cells of children with obstructive sleep apnea[J]. Chest.2008.134(2):324-31.
[34] Carneiro G, Togeiro SM, Ribeiro-Filho FF, et al. Continuous positive airwaypressure therapy improves hypoadiponectinemia in severe obese men withobstructive sleep apnea without changes in insulin resistance[J].Metab Syndr RelatDisord.2009.7(6):537-42.
[35] Gami AS, Caples SM, Somers VK. Obesity and obstructive sleepapnea[J].Endocrinol Metab Clin North Am.2003.32(4):869-94.
[36] Marik PE. Leptin, obesity, and obstructive sleep apnea[J].Chest.2000.118(3):569-71.
[37] Zheng M, Wang M. Study of the relationship between obstructive sleep apneasyndrome and obesity and serum resistin level[J]. Lin Chung Er Bi Yan Hou TouJing Wai Ke Za Zhi.2008.22(2):81-3,94.
[38] Palmer LJ, Buxbaum SG, Larkin E, et al. A whole-genome scan for obstructivesleep apnea and obesity[J]. Am J Hum Genet.2003.72(2):340-50.
[39] Franks PW, Poveda A. review Gene-Lifestyle and Gene-PharmacotherpyInteractions in Obesity and Its Cardiovascular Consequences[J].Curr VascPharmacol.2010.
[40] Busetto L, Enzi G, Inelmen EM, et al. Obstructive sleep apnea syndrome in morbidobesity: effects of intragastric balloon[J].Chest.2005.128(2):618-23.
[41] Weaver JM. Increased anesthetic risk for patients with obesity and obstructivesleep apnea[J].Anesth Prog.2004.51(3):75.
[42] Pillar G, Shehadeh N. Abdominal fat and sleep apnea: the chicken or theegg[J].Diabetes Care.2008.31Suppl2: S303-9.
[43] Popko K, Gorska E, Wasik M, et al. Frequency of distribution of leptin receptorgene polymorphism in obstructive sleep apnea patients[J].J Physiol Pharmacol.2007.58Suppl5(Pt2):551-61.
[44] Huang R, Huang XZ, Li M, Xiao Y, Zhang J. An investigation of the relationshipbetween Lepr gene Gln223Arg polymorphism and obstructive sleep apneahypopnea syndrome[J]. Zhonghua Jie He He Hu Xi Za Zhi.2003.26(9):517-21.
[45] Chilukuri K, Dalal D, Gadrey S, et al. A prospective study evaluating the role ofobesity and obstructive sleep apnea for outcomes after catheter ablation of atrialfibrillation [J]. J Cardiovasc Electrophysiol.2010.21(5):521-5.
[46] Ferguson KA, Ono T, Lowe AA, Ryan CF, Fleetham JA. The relationship betweenobesity and craniofacial structure in obstructive sleep apnea[J].Chest.1995.108(2):375-81.
[47] Czerniawska J, Bielen P, Plywaczewski R, et al. Metabolic abnormalities inobstructive sleep apnea patients[J].Pneumonol Alergol Pol.2008.76(5):340-7.
[48] Ip MS, Lam B, Ng MM, Lam WK, Tsang KW, Lam KS. Obstructive sleep apnea isindependently associated with insulin resistance[J].Am J Respir Crit Care Med.2002.165(5):670-6.
[49] Punjabi NM, Polotsky VY. Disorders of glucose metabolism in sleep apnea[J]. JAppl Physiol.2005.99(5):1998-2007.
[50] Arias MA, Alonso-Fernandez A, Garcia-Rio F. Stroke, obstructive sleep apnea, anddisorders of glucose metabolism. Arch Intern Med.2006.166(13):1418-9; authorreply1419.
[51] Punjabi NM, Shahar E, Redline S, Gottlieb DJ, Givelber R, Resnick HE.Sleep-disordered breathing, glucose intolerance, and insulin resistance: the SleepHeart Health Study[J]. Am J Epidemiol.2004.160(6):521-30.
[52] Yokoe T, Alonso LC, Romano LC, et al. Intermittent hypoxia reverses the diurnalglucose rhythm and causes pancreatic beta-cell replication in mice[J]. J Physiol.2008.586(3):899-911.
[53] Tasali E, Mokhlesi B, Van Cauter E. Obstructive sleep apnea and type2diabetes:interacting epidemics[J]. Chest.2008.133(2):496-506.
[54] Polotsky VY, Patil SP, Savransky V, et al. Obstructive sleep apnea, insulinresistance, and steatohepatitis in severe obesity[J]. Am J Respir Crit Care Med.2009.179(3):228-34.
[55] Kelly A, Dougherty S, Cucchiara A, Marcus CL, Brooks LJ.Catecholamines,adiponectin, and insulin resistance as measured by HOMA in children withobstructive sleep apnea[J]. Sleep.2010.33(9):1185-91.
[56] Folli F, Saad MJ, Kahn CR. Insulin receptor/IRS-1/PI3-kinase signaling system incorticosteroid-induced insulin resistance[J]. Acta Diabetol.1996.33(3):185-92.
[57] Berger D, Barroso I, Soos M, et al. Genetic variants of insulin receptor substrate-1(IRS-1) in syndromes of severe insulin resistance. Functional analysis ofAla513Pro and Gly1158Glu IRS-1[J]. Diabet Med.2002.19(10):804-9.
[58]张杰涛,邱明才.关于糖尿病的几点认识.医学与哲学(临床决策论坛版)[J].2008.(02):18-19.
