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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., (© 2010 The Authors. Journal compilation © 2010 Society for the Study of Addiction.)

To determine whether glycine transporter polymorphisms are associated with alcoholism, three genetic variants of SLC6A5 and two polymorphisms of SLC6A9 were genotyped in 463 German non-alcoholic controls and 644 German alcohol-dependent subjects. Association was investigated employing chi-square statistics and haplotype analysis. There was a significant association between the SLC6A5 polymorphism (rs1443547) and alcohol dependence as alcoholic individuals had a lower rate of AG-allele (chi(2) = 6.048, P = 0.049, d.f. = 2), which did not remain significant after correction for multiple testing. There was no association between SLC6A9 glycine transporter polymorphisms and alcohol dependence, and also none in haplotype analysis.