LACK OF ASSOCIATION BETWEEN THE TRP(64)ARG MUTATION IN THE BETA(3)-ADRENERGIC RECEPTOR GENE AND OBESITY JAPANESE MEN - A LONGITUDINAL ANALYSIS

The beta(3)-adrenergic receptor (beta(3)AR) is implicated in the regul ation of thermogenesis and lipolysis, and it is suggested that the Trp (64)Arg mutation in this receptor may contribute to the development of obesity. To examine whether the Trp(64)Arg mutation had any effect on body weight during adult life, the beta(3)AR genotype was determined in 186 unselected Japanese men, most of whom had records of body weigh t measured yearly from 25-53 yr of age. Of them, 26 subjects were diag nosed as having noninsulin-dependent diabetes mellitus (NIDDM) and 41 as having impaired glucose tolerance. There were 6 subjects (3%) with homozygous mutation, 67 (36%) with heterozygous mutation, and 113 (61% ) with normal allele. Among the 3 genotypes, there were no significant differences in body mass index (BMI) at any age between 25-53 yr and the prevalence of NIDDM at the age of 53 yr. When longitudinal changes in body weight were compared between subjects with and without mutati on, the former were less prone to gain weight than the latter. The fre quency of the mutant allele was 1) not different among obese (BMI, >26 .4), intermediate (BMI, 22-26.4), and nonobese (BMI, <22.0) subjects ( 0.21, 0.22, and 0.26, respectively; P = 0.77); 2) lower in subjects wi th NIDDM than in those without it, but the difference was insignifican t (0.12 us. 0.23; P = 0.07); and 3) similar between 186 unselected men and another group of 100 patients with NIDDM that were randomly selec ted for com parison (0.21 vs. 0.23). These results suggest that the be ta(3)AR is not a major contributing factor to obesity or NIDDM in Japa nese men.