Susceptibility for alcoholism: DRD4 exon III polymorphism: a case-control and a family-based association approach

Abstract The present investigation explored whether the 7-repeat allele of the exon III polymorphism in the dopamine D4 receptor gene confers to susceptibility of alcoholism. Using a classical case-control approach we first compared DRD4 exon III VNTR frequencies between alcoholics and ethnically matched controls (sample I). Secondly, we applied a family-based association approach in an independent parent-offspring sample of alcoholics (sample II). All patients underwent an inpatient treatment for alcohol detoxification: sample I comprised 218 alcoholics and 197 ethnically matched controls, sample II included 76 alcoholics plus their biological parents. A higher proportion of addicted individuals in sample I revealed the 7-repeat allele compared to the control sample yielding an odds ratio (OR) of 1.43 (individuals homozygous for 7-repeat allele) and an OR of 1.69 (homozygous and heterozygous 7-repeat allele individuals together). However, we failed to detect preferential transmission from parents to offspring of either the 7-repeat allele or the long alleles (5-7 repeats) of the DRD4 exon III VNTR in the family-based association approach (sample II). The impact of the DRD4 exon III polymorphism on susceptibility to addictive behaviour putatively plays only a minor role in our sample of alcohol-dependent patients, since we were not able to replicate our findings by the family-based association approach. However, a larger sample size by the family-based approach would be needed (approximately > 300 parent-offspring trios) to definitely corroborate or reject the findings from our case-control sample.