Objective:The authors evaluated the association of three functional promoter polymorphisms of the ADH4 gene with alcohol dependence.Method: DNA from 92 alcohol-dependent patients and 92 healthy comparison subjects was genotyped for all three polymorphisms.Results: Variants at the -75 base-pair (bp) (C allele) and -159 bp (A allele) positions were associated with alcohol dependence. Individuals with haplotypes carrying both risk alleles showed an odds ratio of 2.9. Conclusions:These preliminary results suggest that ADH4 may play a role in the etiology of alcohol dependence. The association requires further study and replication but is functionally plausible and has a large effect size. (Am J Psychiatry 2005; 162:1005-1007)

Among the different possible genes involved in the alcoholism etiology, the X-linked monoamine oxidase A gene is a good candidate. The aim of this study was to assess whether a functional VNTR polymorphism in the promoter region of the monoamine oxidase A gene is associated with alcoholism, comparing patients of both sexes. Ninety-three alcohol-dependent patients (51 males, 42 females) and 93 sex-matched normal controls were engaged. In the total sample, the genotype containing at least one three-repeat allele was significantly more frequent among alcohol-dependent patients than controls (P=0.01). However, when the two sexes were analyzed separately, the difference was statistically significant only for females. This is of particular interest as rates of alcoholism in Brazil are markedly lower in females. Our results suggest that this monoamine oxidase A polymorphism could play a role in susceptibility to alcoholism, which may differ across sexes.