Association of dopamine D2 receptor polymorphisms Ser311Cys and TaqIA withobesity or type 2 diabetes mellitus in Pima Indians

OBJECTIVES: To investigate whether (a) variants within the dopamine D2 rece ptor gene (DRD2) are associated with obesity and type 2 diabetes in Pima In dians, and (b) whether variation in this gene could be responsible for prev iously observed linkage to these phenotypes, at chromosome location 11q23 - 24, in this population. DESIGN: Two single nucleotide polymorphisms (SNPs), Ser311Cys and TaqIA, wi thin the DRD2 gene were genotyped by allelic discrimination PCR in subjects who had provided evidence of linkage to diabetes and obesity in an autosom e-wide scan. SUBJECTS: A total of 1187 subjects were genotyped, including 947 full herit age Pima Indians (80%). Descriptive statistics for all subjects analyzed, f or whom clinical data were available, were (mean+/-s.d.): age at time of la st exam=41+/-15 y; birth year=1950+/-14; age-sex-adjusted body mass index ( BMI; adjusted to a mean age of 35 y) = 36 +/- 8 kg/m(2); male = 44%; diabet ic = 57%. For full heritage Pimas only: age = 43 +/- 15 y; birth year = 194 8 +/- 14; sex-age-adjusted BMI = 36 +/- 8 kg/m(2); male = 43%; diabetic = 5 9%. RESULTS: Neither polymorphism was significantly associated with diabetes in full heritage Pimas. Individuals with a 'CG' genotype at the Ser311Cys SNP had a higher BMI than those with a 'CC' genotype (36.7 vs 35.5 kg/m(2), P = 0.04). Linkage analysis of BMI, adjusted for either polymorphism, resulte d in LOD scores that were similar to those obtained without adjustment. CONCLUSION: Heterozygotes at the Ser311Cys DRD2 polymorphism had a slightly higher BMI than homozygotes, however neither the Ser311Cys nor the TaqIA p olymorphism accounted for the linkage with BMI on chromosome 11 in Pima Ind ians.