Synergistic effect of polymorphisms in uncoupling protein 1 and β3-adrenergic receptor genes on long-term body weight change in Finnish type 2 diabetic and non-diabetic control subjects

OBJECTIVE: To investigate the independent and combined effects of the Trp64Arg polymorphism of the BB-adrenergic receptor (beta(3)AR) gene and the (-3826) A-->G polymorphism of the uncoupling protein 1 (UCP1) gene an body weight change in type 2 diabetic and non-diabetic control subjects during a 10 y follow-up study, DESIGN: Controlled 10 y follow-up study with baseline, 5 and 10 y examinations. SUBJECTS: 70 newly diagnosed, middle-aged type 2 diabetic patients and 123 non-diabetic control subjects Rom eastern Finland. MEASUREMENTS: Anthropometric measurements, blood pressure, oral glucose tolerance test, plasma insulin, plasma C-peptide and HbA(1c). Genotypes by polymerase chain reaction followed by enzymatic digestion. RESULTS: No significant differences were found in the frequencies of the two polymorphisms between diabetic: and control subjects. The polymorphisms were not cross-sectionally or longitudinally associated with body weight or BMI in diabetic or control subjects. When the diabetic and control subjects were analysed together, the change in the mean body weight was significantly greater among the subjects with both polymorphisms (n = 11) than among those with no polymorphisms (n = 103; change in weight 6.5 +/- 2.5% vs -0.2 +/- 0.8%, P = 0.036, and change in Body Mass Index 8.5 +/- 2.6% vs 2.0 +/- 0.8%, P = 0.060, mean +/- s.e.m.). CONCLUSIONS: The simultaneous existence of the two polymorphisms was associated with a tendency to gain weight suggesting a synergistic effect of these polymorphisms on body weight gain.