Interaction among genes influencing ethanol metabolism and sex is association with alcohol use disorders in a Tibet population.
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 >or=10 and 350 control subjects with the AUDIT score <or=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.
Guo
Wanjun
W
Psychiatric Laboratory, Department of Psychiatry, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, P.R. China.
Wang
Qiang
Q
Psychiatric Laboratory, Department of Psychiatry, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, P.R. China.
Lanzi
Gongga
G
Medical School, University of Tibet, Lasha, Tibet, P.R. China.
Luobu
Ouzhu
O
Medical School, University of Tibet, Lasha, Tibet, P.R. China.
Ma
Xiaohong
X
Psychiatric Laboratory, Department of Psychiatry, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, P.R. China.
Wang
Yingcheng
Y
Psychiatric Laboratory, Department of Psychiatry, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, P.R. China.
Zhen
Puo
P
Medical School, University of Tibet, Lasha, Tibet, P.R. China.
Ji
Yulin
Y
Department of Science and Technology, West China Hospital, Sichuan University, Chengdu, P.R. China.
Wei
Geng
G
Department of Mental Health, People's Hospital of Tibet Autonomous Region, Lasha, P.R. China.
Wang
Zheng
Z
Psychiatric Laboratory, Department of Psychiatry, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, P.R. China.|Department of Science and Technology, West China Hospital, Sichuan University, Chengdu, P.R. China.
Deng
Wei
W
Psychiatric Laboratory, Department of Psychiatry, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, P.R. China.
Zhuoma
Basang
B
Medical School, University of Tibet, Lasha, Tibet, P.R. China.
Shi
Xiaoming
X
Medical School, University of Tibet, Lasha, Tibet, P.R. China.
Yan
Chengyin
C
Psychiatric Laboratory, Department of Psychiatry, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, P.R. China.
He
Chan
C
Psychiatric Laboratory, Department of Psychiatry, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, P.R. China.
Liu
Xiehe
X
Psychiatric Laboratory, Department of Psychiatry, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, P.R. China.
Wu
Yuejing
Y
Psychiatric Laboratory, Department of Psychiatry, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, P.R. China.
Luo
Hongrong
H
Psychiatric Laboratory, Department of Psychiatry, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, P.R. China.
Collier
David A
DA
Division of Psychological Medicine, Institute of Psychiatry, King's College, London, UK.|SGDP Centre, Institute of Psychiatry, King's College, London, UK.
Ball
David
D
SGDP Centre, Institute of Psychiatry, King's College, London, UK.
Li
Tao
T
Psychiatric Laboratory, Department of Psychiatry, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, P.R. China.|Division of Psychological Medicine, Institute of Psychiatry, King's College, London, UK.|SGDP Centre, Institute of Psychiatry, King's College, London, UK.
Hu
Xun
X
Psychiatric Laboratory, Department of Psychiatry, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, P.R. China.|Division of Psychological Medicine, Institute of Psychiatry, King's College, London, UK.|SGDP Centre, Institute of Psychiatry, King's College, London, UK.
D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000437:Alcoholism / Q000453:epidemiology / Q000235:genetics*; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000483:Alleles; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D000431:Ethanol / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D008297:Male; D008957:Models, Genetic; D011110:Polymorphism, Genetic; D012737:Sex Factors; D018609:Tibet
D000431:Ethanol; C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase; D019392:Cytochrome P-450 CYP2E1; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial