Genotype Arg/Arg, but not Trp/Arg, of the Trp64Arg Polymorphism of the β3-Adrenergic Receptor Is Associated With Type 2 Diabetes and Obesity in a Large Japanese Sample

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Abstract
OBJECTIVE—Despite a large number of studies, no association of the Trp64Arg polymorphism of the β3-adrenergic receptor gene with obesity and type 2 diabetes has yet to be clearly elucidated. We examined the associations in a large population-based sample. RESEARCH DESIGN AND METHODS—A total of 1,685 subjects (935 women and 750 men, aged 58.7 ± 12.4 years) from a cohort population (n = 3,706) of the Funagata Diabetes Study were divided into three groups according to genotypes: Trp/Trp (n = 1,155), Trp/Arg (n = 486), and Arg/Arg (n = 44). Glucose tolerance was diagnosed according to the 1985 World Health Organization criteria. Subjects who had a BMI ≥30 kg/m2 were considered obese. Associations with the traits related to obesity, diabetes, hypertension, and dyslipidemia were also examined. The χ2 test and analysis of variance were used for the association studies and to assess the differences in the traits’ values, respectively. RESULTS—More subjects with genotype Arg/Arg were obese and had diabetes (13.6% for each) than those with genotype Trp/Trp (3.29%, P < 0.001; and 4.16%, P = 0.007, respectively) or genotype Trp/Arg (2.06%, P < 0.001; and 5.97%, P = 0.051, respectively). No significant differences in the frequencies of occurrence of these conditions were observed between genotypes Trp/Arg and Trp/Trp. Traits related to obesity, such as percent body fat (28.82 ± 7.95 vs. 25.93 ± 7.21, P = 0.038) and BMI (25.07 ± 3.84 vs. 23.63 ± 3.18, P = 0.018), were higher in the genotype Arg/Arg than in the genotype Trp/Trp groups. CONCLUSIONS—Genotype Arg/Arg, but not Trp/Arg, of the β3-adrenergic receptor was associated with both obesity and type 2 diabetes in a large Japanese sample.