Analyses of DRD4 sequence variants in African Americans: Associations with alcohol dependence, personality, and population genetics

There is strong evidence for genetic involvement in individual susceptibility to the multiple effects of alcohol abuse. Alcohol abuse has been shown to cause social and economical dysfunction as well as health problems such as cirrhosis of the liver that leads to morbidity. Genetic polymorphisms within dopamine receptor genes have been associated with alcohol dependence in different human populations.; Five dopamine D4 receptor gene (DRD4) polymorphisms were examined to determine if they contribute to alcohol dependence and related phenotypes in African Americans. Population differences in DRD4 marker allele frequencies were also examined. Fifty-four alcohol dependent African American discordant sib-pairs for alcohol dependence were recruited and the personality dimensions of neuroticism, extraversion, openness, agreeableness, and conscientiousness were measured using the NEO-FFI. Genotyping of five polymorphic sites within the DRD4 gene (120 bp duplication; C-616G; C-521T; T581G; and 48 bp VNTR) was performed using PCR-RFLP and microsatellite analysis.; No association was observed for alcohol dependence and any of the DRD4 markers. There was a strong association observed between the C-521T DRD4 marker and extraversion in the unaffected samples (p = 0.005). Significant differences in allele frequencies were observed between African Americans and other populations (representing Europeans and Asians) for all markers (p < 0.02). Significant differences in allele frequencies were also observed between African Americans and Nigerians at one marker (120 bp dup; p < 0.006). Results suggest that sharp differences in DRD4 marker allele frequencies exist between human populations. This will be important in order to understand the role genes such as DRD4 may play in the etiology of a common disease like alcoholism. This study supports the fact that polymorphisms within the dopamine receptor D4 gene may be contributing to phenotypic variation of alcohol dependence, i.e. age of onset and specific personality disorders.