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Lack of Association between the Trp⁶⁴Arg Mutation in the ß₃-Adrenergic Receptor Gene and Obesity in Japanese Men: A Longitudinal Analysis

Third Department of Internal Medicine (T.N., M.Y., S.K., M.N., N.K., T.A., N.N.), National Defense Medical College, Tokorozawa, Saitama; and the Department of Internal Medicine, Self-Defense Force Central Hospital (A.A., H.Y.), Setagaya, Tokyo, Japan

Address all correspondence and requests for reprints to: Dr. Terumasa Nagase, Third Department of Internal Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan.

The ß₃-adrenergic receptor (ß₃AR) is implicated in the regulation of thermogenesis and lipolysis, and it is suggested that the Trp⁶⁴Arg mutation in this receptor may contribute to the development of obesity. To examine whether the Trp⁶⁴Arg mutation had any effect on body weight during adult life, the ß₃AR genotype was determined in 186 unselected Japanese men, most of whom had records of body weight measured yearly from 25–53 yr of age. Of them, 26 subjects were diagnosed 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 mutation, the former were less prone to gain weight than the latter. The frequency 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 with NIDDM than in those without it, but the difference was insignificant (0.12 vs. 0.23; P = 0.07); and 3) similar between 186 unselected men and another group of 100 patients with NIDDM that were randomly selected for comparison (0.21 vs. 0.23). These results suggest that the ß₃AR is not a major contributing factor to obesity or NIDDM in Japanese men.

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