Association of the Trp64Arg Mutation of the β3-Adrenergic Receptor with Diabetes Mellitus, Impaired Glucose Tolerance and Lifestyle in Japanese Workers

In order to investigate whether the Trp64Arg (a missense mutation of tryptophan for arginine at position 64 codon) polymorphism of the β3-adrenergic receptor (β3-AR) gene is related to the incidence of non-insulin-dependent diabetes mellitus (NIDDM) and impaired glucose tolerance (IGT), a retrospective cohort study among Japanese workers was conducted. The subjects were Japanese workers at an occupational site in Shimane Prefecture. Informed consent was obtained from 492 workers. The baseline data were obtained at the regular health examination in 1992 and a retrospective cohort study was performed for analyzing the incidence of NIDDM and IGT in 1998. The Trp64Arg polymorphism β3-AR gene for each worker was detected by the single strand conformation polymerase analysis. Relative risks were calculated by the logistic regression analysis. The rates of Trp64Trp (TT), Trp64Arg (TA) and Arg64Arg (AA) genotypes were 66.3%, 31.1% and 2.6%, respectively. The relative risk of (TA + AA) against TT for the incidence of NIDDM and IGT by univariate analysis was 1.37 (95% incidence of NIDDM and IGT adjusted for confounders in a multiple logistic regression model including age, gender, family history, body mass index, alcohol consumption, eating habits and exercise was 1.31 (95% confidence interval, 0.65-2.67). The present findings suggested that a weak association between Trp64Arg polymorphism of the β3-AR gene and the incidence of NIDDM and IGT.