BETA(3)-ADRENERGIC RECEPTOR GENE POLYMORPHISM IS NOT A MAJOR GENETIC DETERMINANT OF OBESITY AND DIABETES IN JAPANESE GENERAL-POPULATION

To assess the contribution of a replacement of Trp at codon 64 of beta (3)-adrenergic receptor by Arg to fat distribution and metabolic distu rbances in Japanese general population, we examined the missense mutat ion in 1122 persons consisting of 817 men aged 50.0 +/- 8.9 years and 305 women aged 50.8 +/- 8.5 years in Kyushu, Japan. The incidence of A rg64 allele was 0.21; no age-dependent decrease of the allele frequenc y was observed, suggesting that the mutation was not associated with e arly mortality. The genotype was not significantly correlated with bod y mass index or the thickness of visceral fat estimated by ultrasonogr aphy. Glucose tolerance and glucose-induced insulin secretion were not significantly different among subjects with Trp/Trp, Trp/Arg and Arg/ Arg at codon 64. Although in obese persons the ratio of heterozygotes for the mutation tended to be higher in subjects with impaired glucose tolerance than in subjects with normal glucose tolerance, the tendenc y was not observed in non-obese persons. Furthermore none of 39 non-ob ese individuals homozygous for the mutation was diabetic, whereas two out of six obese homozygous persons were diabetic. These observations suggest that the missense mutation may not be a main determinant of ob esity in populations taking low fat/low energy Japanese-style diet and it may not be deleterious at least in non-obese individuals. (C) 1997 Elsevier Science Ireland Ltd.