PREVALENCE OF THE TRP64ARG MISSENSE MUTATION OF THE BETA(3)-ADRENERGIC RECEPTOR GENE IN JAPANESE SUBJECTS

Prompted by the recent findings that a tryptophan to arginine (Trp64Ar g) mutation in the beta(3)-adrenergic receptor gene was associated wit h an earlier onset of non-insulin-dependent diabetes mellitus (NIDDM) in Pima Indians, with abdominal obesity and insulin resistance in Finn s, and with an increased capacity to gain weight in French whites, we studied the prevalence of this mutation in 231 diabetic and 95 nondiab etic Japanese subjects and assessed its contribution to the developmen t of obesity and NIDDM. The allelic frequencies of the mutation were 0 .18 in diabetic and 0.23 in nondiabetic subjects, showing no significa nt difference between the two groups (P = .067). In nondiabetic subjec ts, body mass index (BMI) did not differ between those with and withou t the mutation (22.2 +/- 3.5 v 21.4 +/- 3.2 kg/m(2), P = .252). In NID DM subjects, BMI at the time of study and maximal BMI before the start of treatment did not differ between those with and without the mutati on (22.8 +/- 2.6 v 23.2 +/- 3.7 kg/m(2), P = .678, and 24.7 +/- 2.6 v 24.9 +/- 3.1 kg/m(2), P = .277). Homozygotes for the mutation did not have trends to have increased BMI in either diabetic or nondiabetic su bjects. The age at diagnosis of NIDDM also did not differ between the two groups (48.8 +/- 9.9 v 47.8 +/- 12.5 years, P = .796). Fasting ser um cholesterol and triglyceride levels and systolic and diastolic bloo d pressure before the start of treatment did not differ between NIDDM subjects with and without the mutation. In conclusion, although the Tr p64Arg mutation is not uncommon in Japanese, it does not appear to be associated with obesity, NIDDM, age at diagnosis of NIDDM, or dyslipid emia. Our results suggest that the mutation has minor effects, if any, on the development of obesity and NIDDM in Japanese. Copyright (C) 19 97 by W.B. Saunders Company.