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

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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.

Keywords: ADH4; ADH4 haplotype analysis; Cloninger subtypes; alcohol dependence; alcohol dependence-related phenotypes; association genetic variants

Document Type: Research Article


Affiliations: 1: Department of Psychiatry, Psychosomatics and Psychotherapy, University Medical Center, Regensburg, Germany, 2: Department of Psychiatry and Psychotherapy, Ludwig-Maximilians University, Munich, Germany, 3: Department of Psychiatry and 4: Pomeranian Medical University, Szczecin, Poland, Department of Psychiatry, Johannes-Gutenberg University, Mainz, Germany, 5: Department of Psychiatry, Paracelsus-University, Salzburg, Austria and 6: International Hereditary Cancer Research,

Publication date: 2011-04-01

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