Variant alleles of the D2 dopamine receptor gene and obesity

Abstract 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 ( DRD 2) gene and the number of receptor binding sites in vulnerability to substance abuse and obesity. We recently demonstrated that the A1 and B1 genotypes are in linkage disequilibrium and predictive of smoking status. Previous studies have evaluated the relationship between obesity and A1 but not B1 genotypes. Our objective was to assess the relationships between obesity and DRD 2 Taq I A and Taq I B genotypes in healthy individuals. Subjects were 139 Caucasian average weight and 37 obese individuals (body mass index ⩾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 A1 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 DRD 2 A1 genotypes was 3.48 (95% confidence intervals=1.55, 7.80), compared with 4.55 (1.94, 10.69) for the DRD 2 B1 genotypes. Individuals who had the A1 or B1 genotypes had higher BMI than those with the wildtype genotypes (P=0.086 and 0.05 respectively). The prevalence of the A1 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 B1 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.