Variant alleles of the D2 dopamine receptor gene and obesity

The mesocorticolimbic dopaminergic reward pathways have a role in the neuromodulation of appetite. There are data supporting a role of allelic variants of the D2 dopamine receptor (DRD2) gene and the number of receptor binding sites in vulnerability to substance abuse and obesity. We recently demonstrated that the Al and B1 genotypes are in linkage disequilibrium and predictive of smoking status. Previous studies have evaluated the relationship between obesity and AI but not B1 genotypes. Our objective was to assess the relationships between obesity and DRD2 TaqI A and TaqI B genotypes in healthy individuals. Subjects were 139 Caucasian average weight and 37 obese individuals (body mass index greater than or equal to 30) identified as comparison subjects for ongoing case-control studies. Among the obese group, only 41.7% exhibited the A2 genotypes and 58.3% the Al genotypes compared with 68.8% and 31.2% respectively for the average weight subjects (P=0.002). There was a similar pattern for B2 genotypes (51.4% compared with 78.9% respectively, P=0.003). The risk of obesity associated with the DRD2 Al genotypes was 3.48 (95% confidence intervals = 1.55, 7.80), compared with 4.55 (1.94, 10.69) for the DRD2 B1 genotypes. Individuals who had the Al or BI genotypes had higher BMI than those with the wildtype genotypes (P=0.086 and 0.05 respectively). The prevalence of the Al genotypes was' 2 of 5 (40%) obese individuals who never smoked, 12 of 22 (54.6%) for obese former smokers, and 7 of 9 (77.9%) for obese current smokers. The comparable percentages for the BI genotypes were 0%, 56.5% and 55.6%. Further emphasis needs to be placed on identifying the genetic basis for obesity in order to develop targeted weight reduction interventions, that may improve potential for success. (C) 2000 Elsevier Science Inc.