Premium
Interaction among genes influencing ethanol metabolism and sex is association with alcohol use disorders in a Tibet population
Author(s) -
Guo Wanjun,
Wang Qiang,
Lanzi Gongga,
Luobu Ouzhu,
Ma Xiaohong,
Wang Yingcheng,
Zhen Puo,
Ji Yulin,
Wei Geng,
Wang Zheng,
Deng Wei,
Zhuoma Basang,
Shi Xiaoming,
Yan Chengyin,
He Chan,
Liu Xiehe,
Wu Yuejing,
Luo Hongrong,
Collier David A,
Ball David,
Li Tao,
Hu Xun
Publication year - 2010
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.31020
Subject(s) - adh1b , aldh2 , allele , genotype , cyp2e1 , ethanol metabolism , genetics , population , medicine , biology , gene , environmental health , metabolism , cytochrome p450 , enzyme , biochemistry , branched chain alpha keto acid dehydrogenase complex , dehydrogenase
Associations between alcohol use disorders and polymorphisms of genes influencing ethanol metabolism have been widely reported, but gene–gene and gene–sex interaction studies have rarely been examined. Using a set of samples collected during an epidemiological study of alcohol use disorders AUDs in a Tibetan population in China, we performed a case–control study to investigate the relationship between the functional polymorphisms of genes influencing ethanol metabolism and AUDs. The sample included 383 individuals with an AUDIT score ≥10 and 350 control subjects with the AUDIT score ≤5. All participants were genotyped for ALDH2*1/*2, ADH1B*1/*2, and CYP2E1*c1/c2*. Data were analyzed employing an integrated strategy using MDR, SPSS, and UNPHASED software. The MDR analysis showed that the four‐factor model including ADH1B*1/*2, ALDH2*1/*2, and CYP2E1*c1/*c2 polymorphisms, and sex was the most accurate model associated with AUDs with the highest OR 3.299. It also revealed that CYP2E1 *c1/*c2 polymorphism interacted significantly with sex. Independent analysis confirmed that both ADH2*2 and ALDH2*2 allele were significantly associated with AUDs (OR: 0.441 for ADH2*2 and 0.137 for ALDH2*2). CYP2E1*c2 was positively associated with AUDs only in males homozygotic for ALDH2*1 and ADH1B*1 (OR: 2.585). Cumulative association analysis showed the number of protective alleles and genotypes were negatively associated with AUDs. In conclusion, ALDH2*2 and ADH1B*2 alleles were not only independently associated with AUDs but also demonstrated cumulative dosage effects. However the positive association between CYP2E1*c2 allele and AUDs might only exist in males homozygotic for ALDH2*1 and ADH1B*1. © 2009 Wiley‐Liss, Inc.