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

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.