Association of ADH4 genetic variants with alcohol dependence risk and related phenotypes: results from a larger multicenter association study

作者：Preuss Ulrich W^*; Ridinger Monika; Rujescu Dan; Samochowiec Jerzy; Fehr Christoph; Wurst Friedrich M; Koller Gabriele; Bondy Brigitta; Wodarz Norbert; Debniak Tadeusz; Grzywacz Anna; Soyka Michael; Zill Peter

来源：ADDICTION BIOLOGY, 2011, 16(2): 323-333.

DOI：10.1111/j.1369-1600.2010.00236.x

• ADH4
• alcohol dependence
• alcohol dependence-related phenotypes
• association genetic variants
• Cloninger subtypes
• ADH4 haplotype analysis

Genetic variants of the alcohol-metabolizing enzyme ADH4, located on chromosome 4q22-4q23, have been related to alcohol dependence (AD) risk in previous research. The aim of this association study in a large multicenter sample of alcohol-dependent individuals and controls is to confirm ADH4 single nucleotide polymorphism (SNP) and haplotype association with AD and relevant related phenotypes. One thousand, six hundred and twenty-two (1622) inpatient subjects and 1469 control subjects with DSM-IV. AD from four addiction treatment centres were included. Characteristics of AD and related phenotypes including alcohol withdrawal, Cloninger's type I and II and first ages of drinking, regular drinking and AD onset were obtained using standardized structured interviews. After subjects were genotyped for 2 ADH4 polymorphisms, single SNP case-control and haplotype analyses were conducted. Both variants-rs1800759 and rs1042364-and the A-A and C-G haplotypes were significantly related to AD across samples. Furthermore, associations with AD-related phenotypes and subtypes revealed a potential protective influence of this haplotype. This study confirms the significant relationship of ADH4 variants with AD and related phenotypes. While the rs1800759 and rs1042364 A-A haplotype had a potential protective influence on the risk for several AD-related phenotypes, this effect is rather small compared to functional variants of other alcohol or acetaldehyde-metabolizing enzymes like ALDH2*2 or ADH1B*2.

• 出版日期2011-4