THE SIGNIFICANCE OF THE TRP-64 ARG MUTATION OF THE BETA-3-ADRENERGIC RECEPTOR GENE IN IMPAIRED GLUCOSE-TOLERANCE, NON-INSULIN-DEPENDENT DIABETES-MELLITUS, AND INSULIN-RESISTANCE IN JAPANESE SUBJECTS

It has been reported that the Trp 64 Arg mutation of the human beta(3) -adrenergic receptor (beta(3)-AR) gene is related to an earlier age of onset of non-insulin-dependent diabetes mellitus (NIDDM) and features of insulin resistance and weight gain in morbidly obese patients. How ever, such findings have not been consistent in varying ethnic populat ions. In the present study, we investigated the frequency of the Trp 6 4 Arg mutation of the human beta(3)-AR gene in Japanese control subjec ts (n = 253) and in NIDDM (n = 314) and impaired glucose tolerance (IG T) patients (n = 100). We compared the frequency of the mutation with the body-mass index (BMI) in these groups and with the metabolic clear ance rate (MCR) of glucose in the NIDDM patients. A Trp 64 Arg mutatio n was observed in 36.7%, 31.6%, and 37.0% of the control, NIDDM, and I GT subjects, respectively. The frequency of the homozygotes for the mu tation was 4.3%, 4.8%, and 3.0%, respectively. Neither the genotype fr equency (Trp/Arg, Arg/Arg) nor the frequency of the mutated allele was significantly different among the three groups. The BMI of the subjec ts with the mutation was not significantly higher than that of the sub jects without the mutation in each group. Furthermore, the allele freq uency (A) was not different among the subjects with different BMIs (BM I < 22.0, 22.0 less than or equal to BMI less than or equal to 26.4, B MI > 26.4) in each group. In a separate group of NIDDM patients, the M CR of the subjects with intermediate BMIs (22.0 less than or equal to BMI less than or equal to 26.4) with the mutation tended to be lower t han that of those without the mutation. In addition, the MCR of the su bjects with the mutation in this group was significantly lower compare d with that of those with a BMI less than 22. These results indicate t hat the Trp 64 Arg mutation of the beta(3)-AR gene may not contribute to the development of NIDDM or be a determinant of obesity in the Japa nese population. However, the mutation may contribute to insulin resis tance in NIDDM patients with an intermediate BMI. Copyright (C) 1998 b y W.B. Saunders Company.