Frequency of and interaction between polymorphisms in the β3-adrenergic receptor and in uncoupling proteins 1 and 2 and obesity in Germans

OBJECTIVE: To determine the role of polymorphisms in the genes for beta 3-adrenergic receptor (beta 3-AR) and in uncoupling proteins 1 and 2 (UCP-1, UCP-2) in obesity, DESIGN: Association study with three polymorphisms and obesity. SUBJECTS: Two hundred and thirty-six morbidly obese patients who underwent gastric banding surgery, 381 patients from the medical clinic and 198 healthy blood donors. MEASUREMENTS: The frequencies of the W64R in beta 3-AR, the -3826A-->G in UCP-1 and the 45 bp insertion in the 3 untranslated region of exon 8 in UCP-2 polymorphisms were determined. RESULTS: There were no significant differences in the frequencies of the beta 3-AR and UCP-1 polymorphisms between obese (body mass index, BMI > 30 kg/m(2)) and lean subjects. Lean, but not obese, carriers of the R allele of beta 3-AR had a significantly higher BMI. The mean age of obese subjects (excluding diabetics) who were carriers of the G allele of the UCP-1 polymorphism, 36 y, was significantly younger than wild-type, 40 y (P = 0.007), This effect was not seen in lean subjects. The effect of the G allele on the mean age of obese subjects was more apparent in subjects who were also carriers of the R allele of the beta 3-AR polymorphism. The frequency of the ins allele of UCP-2 was significantly higher in obese subjects, 0.31, than in lean, 0.24 (P = 0.002) and carriers of the ins allele had a significantly higher BMI, 38 vs 35 (P = 0.005). There was no association between any of the polymorphisms and type II diabetes. CONCLUSION: In a German population, there was no association between the W64R in beta 3-AR or the -3826A-->G in UCP-1 polymorphisms and obesity. However, they act synergistically to accelerate the development of obesity. The 45 bp insertion in the 3' untranslated region of exon 8 in UCP-2 polymorphism is associated with obesity.