title: Gender-specific interactions between alcohol metabolism genes and severity of quantitative alcohol-related-traits in a Tibetan population.
abstract: Association between genes influencing alcohol metabolism and alcohol use disorders (AUD) has been extensively studied, but the effect of interactions between these genes and AUD have rarely been tested. Our previous case-control study in a Tibetan population noted that the positive association between c2 allele of cytochrome P4502E1 (CYP2E1) gene and AUD might only exist in males who are homozygotes for 1 alleles of aldehyde dehydrogenase-2 (ALDH2) and alcohol dehydrogenase-1B (ADH1B) genes, but this interaction did not reach statistical significance. Using the same set of data, the present study was aimed at exploring interactions between these genes and quantitative alcohol-related-trait scores (QARTs), and whether these are influenced by gender. The sample included 383 AUD cases with the alcohol use disorders identification test (AUDIT) score ≥10 and 350 normal controls with the AUDIT score ≤5. QARTs were measured using three factors from AUDIT. Possible associations of QARTs with interactions among genotypes of ALDH2 1/ 2, ADH1B1/2 and CYP2E1 c1/c2 and sex were analyzed in AUD cases and normal controls separately. The subjects with 2 alleles of ALDH2 or/and ADH1B had significantly lower scores of alcohol intake among controls but had significantly higher scores of alcohol related problems among cases. The score of alcohol intake in male cases who are homozygous for ALDH2 1 and ADH1B 1 and with CYP2E1 c2 allele was significantly higher than that of other cases. These findings suggest that interactions between genes influencing alcohol metabolism are influenced by gender and might affect QARTs differently between the milder-/non-drinkers and AUD cases.
authors.affiliation: Mental Health Centre Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Wan-Jun
authors.initials: WJ
authors.lastname: Guo
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Gongga
authors.initials: G
authors.lastname: Lanzi
authors.forename: Ouzhu
authors.initials: O
authors.lastname: Luobu
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Ma
authors.forename: Ying-Cheng
authors.initials: YC
authors.lastname: Wang
authors.forename: Puo
authors.initials: P
authors.lastname: Zhen
authors.forename: Geng
authors.initials: G
authors.lastname: Wei
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.forename: Basang
authors.initials: B
authors.lastname: Zhuoma
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Shi
authors.forename: Xie-He
authors.initials: XH
authors.lastname: Liu
authors.forename: Yue-Jing
authors.initials: YJ
authors.lastname: Wu
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: David A
authors.initials: DA
authors.lastname: Collier
authors.forename: David
authors.initials: D
authors.lastname: Ball
authors.forename: Xun
authors.initials: X
authors.lastname: Hu
authors.forename: Tao
authors.initials: T
authors.lastname: Li
mesh_terms: D000437:Alcoholism / Q000208:ethnology / Q000235:genetics*; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000080924:Aldehyde Dehydrogenase 1 Family; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D044466:Asian People; D016022:Case-Control Studies; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D000431:Ethanol / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D019655:Quantitative Trait, Heritable; D050697:Retinal Dehydrogenase / Q000235:genetics*; D012737:Sex Factors; D018609:Tibet / Q000453:epidemiology
chemical_list: D007527:Isoenzymes; D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1; D000080924:Aldehyde Dehydrogenase 1 Family; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase