武汉地区汉族人群ALDH2基因多态性的分布研究
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摘要
目的研究湖北武汉地区汉族人群中的乙醛脱氢酶2(ALDH2)*2等位基因及基因型的频率分布特征。方法利用基因芯片杂交技术检测样本基因型,对465名(262名男性,203名女性)湖北武汉地区汉族人群进行ALDH2*2基因多态性分析,将结果与文献报道的其他地区及不同民族进行比较,并比较本地区不同性别间基因多态性的差异。结果 465名武汉地区汉族人群中ALDH2*1和*2等位基因频率分别为80.22%和19.78%;湖北武汉地区汉族人群ALDH2基因型与洛阳、青岛、上海等城市地区的人群间差异无统计学意义(P> 0.05);不同民族间ALDH2等位基因和基因型各不相同,武汉地区汉族人群与壮族、维族、朝鲜族和鄂伦春族地区人群的差异具有统计学意义(P <0.05),与藏族、回族、蒙族和白族地区人群的差异无统计学意义(P> 0.05);不同国家之间比较,中国人群ALDH2等位基因及基因型频率与日本、印度、土耳其和美国人群的差异具有统计学意义(P <0.05);不同性别比较,男性与女性ALDH2等位基因与基因表型间差异无统计学意义(P> 0.05)。结论 ALDH2*2基因多态性分布在不同民族和国家之间差异具有统计学意义,而在不同地区和不同性别之间差异不具有统计学意义。
Objective To identify allele and genotype distribution of aldehyde dehydrogenase 2(ALDH2)*2 among the Han population in Wuhan. Methods Genotype of the samples were identified by gene chip technology. The allele and genotype distribution of ALDH2*2 of 465 samples(262 males and 203 females) from Wuhan were analyzed and compared with those of other regions and other ethnic groups. Results Frequencies of ALDH2*1 and ALDH2*2 alleles were 80.22% and 19.78%. Compared with those of other regions and other ethnic groups, the frequencies of ALDH2 genotypes showed no statistic difference with those in other cities(P> 0.05). The distribution of gene polymorphisms in Han population showed a significant difference with that of Zhuang, Uygurs, Chaoxian and Orequn ethnic groups(P < 0.05), but no difference with that in Zang, Hui, Mongolian and Bai ethnic groups(P > 0.05). Compared with different countries, the allele and frequencies of ALDH2 in Chinese were significantly different from those in Japan, India, Turkey and the United States(P< 0.05). There was no significant difference in ALDH2 alleles and genotypes between males and females(P> 0.05). Conclusion The polymorphism of ALDH2*2 is statistically significant in different ethnic groups and countries, but no significant difference in regions or genders.
Objective To identify allele and genotype distribution of aldehyde dehydrogenase 2(ALDH2)*2 among the Han population in Wuhan. Methods Genotype of the samples were identified by gene chip technology. The allele and genotype distribution of ALDH2*2 of 465 samples(262 males and 203 females) from Wuhan were analyzed and compared with those of other regions and other ethnic groups. Results Frequencies of ALDH2*1 and ALDH2*2 alleles were 80.22% and 19.78%. Compared with those of other regions and other ethnic groups, the frequencies of ALDH2 genotypes showed no statistic difference with those in other cities(P> 0.05). The distribution of gene polymorphisms in Han population showed a significant difference with that of Zhuang, Uygurs, Chaoxian and Orequn ethnic groups(P < 0.05), but no difference with that in Zang, Hui, Mongolian and Bai ethnic groups(P > 0.05). Compared with different countries, the allele and frequencies of ALDH2 in Chinese were significantly different from those in Japan, India, Turkey and the United States(P< 0.05). There was no significant difference in ALDH2 alleles and genotypes between males and females(P> 0.05). Conclusion The polymorphism of ALDH2*2 is statistically significant in different ethnic groups and countries, but no significant difference in regions or genders.
引文
[1]Mackenzie IS,Maki-Petaja KM,McEniery CM,et al.Aldehyde dehydrogenase 2 plays a role in the bioactivation of nitroglycerin in humans[J]. Arterioscler Thromb Vasc Biol,2005,25(9):1891-1895.
[2]Chen Z,Foster MW,Zhang J,et al. An essential role for mitochondrial aldehyde dehydrogenase in nitroglycerin bioactivation[J]. Proc Natl Acad Sci USA,2005,102(34):12159-12164.
[3]Yoshida AR,Huang IY,Ikawa M. Molecular abnormality of an inactive aldehyde dehydrogenase variant commonly found in Orientals[J]. Proc Natl Acad Sci USA,1984,81(1):258-261.
[4]Crabb DW,Edenberg HJ,Bosron WF,et al. Genotypes for aldehyde dehydrogenase deficiency and alcohol sensitivity. The inactive ALDH2*2 allele is dominant[J]. J Clin Invest,1989,83(1):314-316.
[5]Li Y,Zhang D,Jin W,et al. Mitochondrial aldehyde dehydrogenase-2(ALDH2)Glu504Lys polymorphism contributes to the variation in efficacy of sublingual nitroglycerin[J]. J Clin Invest,2006,116(2):506-511.
[6]Lai CL,Yao CT,Chau GY,et al. Dominance of the inactive Asian variant over activity and protein contents of mitochondrial aldehyde dehydrogenase 2 in human liver[J].Alcohol Clin Exp Res,2014,38(1):44-50.
[7]Bosron WF,Lumeng L,Li TK. Genetic polymorphism of enzymes of alcohol metabolism and susceptibility to alcoholic liver disease[J]. Mol Aspects Med,1988,10(2):147-158.
[8]Druesne-Pecollo N,Tehard B,Mallet Y,et al. Alcohol and genetic polymorphisms:effect on risk of alcohol-related cancer[J]. Lancet Oncol,2009,10(2):173-180.
[9]Matsuo K,Oze I,Hosono S,et al. The aldehyde dehydrogenase 2(ALDH2)Glu504Lys polymorphism interacts with alcohol drinking in the risk of stomach cancer[J]. Carcinogenesis,2013,34(7):1510-1515.
[10]Yu C,Guo Y,Bian Z,et al. Association of low-activity ALDH2 and alcohol consumption with risk of esophageal cancerinChineseadults:Apopulation-basedcohort study[J]. Int J Cancer,2018,143:1652-1661.
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[12]Xu F,Chen YG,Xue L,et al. Role of aldehyde dehydrogenase 2 Glu504lys polymorphism in acute coronary syndrome[J]. J Cell Mol Med,2011,15(9):1955-1962.
[13]Xu F,Sun Y,Shang R,et al. The Glu504Lys polymorphism of aldehyde dehydrogenase 2 contributes to development of coronary artery disease[J]. Tohoku J Exp Med,2014,234(2):143-150.
[14]Li H,Borinskaya S,Yoshimura K,et al. Refined geographic distribution of the oriental ALDH2*504Lys(nee487Lys)variant[J]. AnnHumGen,2009,73(3):335-345.
[15]张竹梅,刘茶珍,边建超,等.洛阳市汉族群体ADH2和ALDH2的基因多态性研究[J].遗传,2009,24(5):532-536.
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[17]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.
[18]刘燕,王朝才,李斌,等.西宁市汉族人群乙醛脱氢酶2基因多态性分布与饮酒行为的关系[J].青海医学院学报,2013,334(1):42-45.
[19]袁青,薛亚东,郑雅萍,等.浙江金华地区汉族ALDH2基因多态性与胃癌易感性调查[J].中国地方病防治杂志,2016,31(2):153-155.
[20]李克明,唐汉庆,赵玉峰,等.右江流域壮族人群酒精依赖程度与ADH和ALDH2基因多态性的关联性研究[J].右江医学,2017,45(1):29-31.
[21]刘燕,王朝才,梁军,等.青海地区藏族与汉族人群酒精性肝病与乙醛脱氢酶2基因多态性关系[J].青海医学院学报,2014,35(2):92-94.
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[23]范建华,沈渔,崔玉华,等.朝鲜族、鄂伦春族醇代谢酶基因多态性与酒依赖的研究[J].中华精神科杂志,1998,31(4):209-212.
[24]ZhangLQ,SongX,ZhaoXK,etal. Associationof genotypes of rs671 within with risk for gastric cardia adenocarcinoma in the Chinese Han population in high-and low-incidence areas[J]. Cancer Biol Med,2017,14(1):60-65.
[25]MasaokaH,ItoH,GallusS,etal.Combinationof ALDH2 and ADH1B polymorphisms is associated with smoking initiation:A large-scale cross-sectional study in a Japanese population[J]. Drug Alcohol Depend,2017,173:85-91.
[26]Kang TS,Woo SW,Park HJ,et al. Comparison of genetic polymorphisms of CYP2E1,ADH2,and ALDH2genes involved in alcohol metabolism in Koreans and four other ethnic groups[J]. J Clin Pharm Ther,2009,34(2):225-230.
[27]Abdul AM,Subodh KJ. ADH1B,ALDH2,GSTM1 and GSTT1 gene polymorphic frequencies among alcoholics and controls in the Arcadian population of central India[J].Asia Pac J Cancer P,2018,19(3):725-731.
[28]Zeliha K,Tulin S. Distribution of ADH1B,ALDH2,CYP2E1*6,and CYP2E1*7B genotypes in Turkish population[J]. Alcohol,2010,44(5):415-423.
[29]Wan YJ,Poland RE,Lin KM. Genetic polymorphism of CYP2E1,ADH2,and ALDH2 in Mexican-Americans[J].Genet Test,1998,2(1):79-83.
[30]Khazim K,Azulay EE,Kristal B,et al. Interleukin 1gene polymorphism and susceptibility to disease[J]. Immunol Rev,2018,281(1):40-56.
[31]Dong AN,TanBH,Pan Y,etal.CytochromeP450genotype-guided drug therapies:an update on current states[J].ClinExpPharmacolPhysiol,2018,doi:10.1111/1440-1681.12978.
[32]Morita K,Masuda N,Oniki K,et al. Association between the aldehyde dehydrogenase 2*2 allele and smoking-related chronic airway obstruction in Japanese general population:a pilot study[J]. Toxicol Lett,2015,236(2):117-122.
[33]Wu Y,Ni J,Cai X,et al. Positive association between ALDH2 rs671 polymorphism and essential hypertension:A case-control study and meta-analysis[J]. PLoS One,2017,12(5):e0177023.
[2]Chen Z,Foster MW,Zhang J,et al. An essential role for mitochondrial aldehyde dehydrogenase in nitroglycerin bioactivation[J]. Proc Natl Acad Sci USA,2005,102(34):12159-12164.
[3]Yoshida AR,Huang IY,Ikawa M. Molecular abnormality of an inactive aldehyde dehydrogenase variant commonly found in Orientals[J]. Proc Natl Acad Sci USA,1984,81(1):258-261.
[4]Crabb DW,Edenberg HJ,Bosron WF,et al. Genotypes for aldehyde dehydrogenase deficiency and alcohol sensitivity. The inactive ALDH2*2 allele is dominant[J]. J Clin Invest,1989,83(1):314-316.
[5]Li Y,Zhang D,Jin W,et al. Mitochondrial aldehyde dehydrogenase-2(ALDH2)Glu504Lys polymorphism contributes to the variation in efficacy of sublingual nitroglycerin[J]. J Clin Invest,2006,116(2):506-511.
[6]Lai CL,Yao CT,Chau GY,et al. Dominance of the inactive Asian variant over activity and protein contents of mitochondrial aldehyde dehydrogenase 2 in human liver[J].Alcohol Clin Exp Res,2014,38(1):44-50.
[7]Bosron WF,Lumeng L,Li TK. Genetic polymorphism of enzymes of alcohol metabolism and susceptibility to alcoholic liver disease[J]. Mol Aspects Med,1988,10(2):147-158.
[8]Druesne-Pecollo N,Tehard B,Mallet Y,et al. Alcohol and genetic polymorphisms:effect on risk of alcohol-related cancer[J]. Lancet Oncol,2009,10(2):173-180.
[9]Matsuo K,Oze I,Hosono S,et al. The aldehyde dehydrogenase 2(ALDH2)Glu504Lys polymorphism interacts with alcohol drinking in the risk of stomach cancer[J]. Carcinogenesis,2013,34(7):1510-1515.
[10]Yu C,Guo Y,Bian Z,et al. Association of low-activity ALDH2 and alcohol consumption with risk of esophageal cancerinChineseadults:Apopulation-basedcohort study[J]. Int J Cancer,2018,143:1652-1661.
[11]Mackenzie IS,Maki-Petaja KM,McEniery CM,et al. Aldehyde dehydrogenase 2 plays a role in the bioactivation of nitroglycerin in humans[J]. Arterioscler Thromb Vasc Biol,2005,25(9):1891-1895.
[12]Xu F,Chen YG,Xue L,et al. Role of aldehyde dehydrogenase 2 Glu504lys polymorphism in acute coronary syndrome[J]. J Cell Mol Med,2011,15(9):1955-1962.
[13]Xu F,Sun Y,Shang R,et al. The Glu504Lys polymorphism of aldehyde dehydrogenase 2 contributes to development of coronary artery disease[J]. Tohoku J Exp Med,2014,234(2):143-150.
[14]Li H,Borinskaya S,Yoshimura K,et al. Refined geographic distribution of the oriental ALDH2*504Lys(nee487Lys)variant[J]. AnnHumGen,2009,73(3):335-345.
[15]张竹梅,刘茶珍,边建超,等.洛阳市汉族群体ADH2和ALDH2的基因多态性研究[J].遗传,2009,24(5):532-536.
[16]乔立群,葛银林,芦庭秀,等.青岛市汉族群体ADH2和ALDH2基因多态性及其与乙醇代谢速率关系[J].青岛大学医学院学报,2014,50(4):299-302.
[17]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.
[18]刘燕,王朝才,李斌,等.西宁市汉族人群乙醛脱氢酶2基因多态性分布与饮酒行为的关系[J].青海医学院学报,2013,334(1):42-45.
[19]袁青,薛亚东,郑雅萍,等.浙江金华地区汉族ALDH2基因多态性与胃癌易感性调查[J].中国地方病防治杂志,2016,31(2):153-155.
[20]李克明,唐汉庆,赵玉峰,等.右江流域壮族人群酒精依赖程度与ADH和ALDH2基因多态性的关联性研究[J].右江医学,2017,45(1):29-31.
[21]刘燕,王朝才,梁军,等.青海地区藏族与汉族人群酒精性肝病与乙醛脱氢酶2基因多态性关系[J].青海医学院学报,2014,35(2):92-94.
[22]曹西蓉,吴德生.中国五个民族人群样本中酒精代谢相关酶基因多态性分布比较[J].卫生研究,2002,31(3):156-159.
[23]范建华,沈渔,崔玉华,等.朝鲜族、鄂伦春族醇代谢酶基因多态性与酒依赖的研究[J].中华精神科杂志,1998,31(4):209-212.
[24]ZhangLQ,SongX,ZhaoXK,etal. Associationof genotypes of rs671 within with risk for gastric cardia adenocarcinoma in the Chinese Han population in high-and low-incidence areas[J]. Cancer Biol Med,2017,14(1):60-65.
[25]MasaokaH,ItoH,GallusS,etal.Combinationof ALDH2 and ADH1B polymorphisms is associated with smoking initiation:A large-scale cross-sectional study in a Japanese population[J]. Drug Alcohol Depend,2017,173:85-91.
[26]Kang TS,Woo SW,Park HJ,et al. Comparison of genetic polymorphisms of CYP2E1,ADH2,and ALDH2genes involved in alcohol metabolism in Koreans and four other ethnic groups[J]. J Clin Pharm Ther,2009,34(2):225-230.
[27]Abdul AM,Subodh KJ. ADH1B,ALDH2,GSTM1 and GSTT1 gene polymorphic frequencies among alcoholics and controls in the Arcadian population of central India[J].Asia Pac J Cancer P,2018,19(3):725-731.
[28]Zeliha K,Tulin S. Distribution of ADH1B,ALDH2,CYP2E1*6,and CYP2E1*7B genotypes in Turkish population[J]. Alcohol,2010,44(5):415-423.
[29]Wan YJ,Poland RE,Lin KM. Genetic polymorphism of CYP2E1,ADH2,and ALDH2 in Mexican-Americans[J].Genet Test,1998,2(1):79-83.
[30]Khazim K,Azulay EE,Kristal B,et al. Interleukin 1gene polymorphism and susceptibility to disease[J]. Immunol Rev,2018,281(1):40-56.
[31]Dong AN,TanBH,Pan Y,etal.CytochromeP450genotype-guided drug therapies:an update on current states[J].ClinExpPharmacolPhysiol,2018,doi:10.1111/1440-1681.12978.
[32]Morita K,Masuda N,Oniki K,et al. Association between the aldehyde dehydrogenase 2*2 allele and smoking-related chronic airway obstruction in Japanese general population:a pilot study[J]. Toxicol Lett,2015,236(2):117-122.
[33]Wu Y,Ni J,Cai X,et al. Positive association between ALDH2 rs671 polymorphism and essential hypertension:A case-control study and meta-analysis[J]. PLoS One,2017,12(5):e0177023.