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Meta-Analysis of the Association of Trp⁶⁴Arg Polymorphism of ß₃-Adrenergic Receptor Gene with Body Mass Index¹

Department of Geriatric Medicine, Osaka University Medical School, Osaka, Japan

Address all correspondence and requests for reprints to: Hiroshi Ikegami, M.D., Ph.D., Department of Geriatric Medicine, Osaka University Medical School, 2–2 Yamadaoka, Suita, Osaka 565, Japan. E-mail: ikegami{at}geriat.med.osaka-u.ac.jp

A possible pathogenic polymorphism in the ß₃-adrenergic receptor gene (Trp⁶⁴Arg) has been reported to be associated with increased body weight, clinical features of insulin resistance, and early development of type 2 diabetes mellitus in several populations. However, such findings have not been consistent among studies, making the hypothesis that this genetic marker is associated with clinical features controversial. To assess the effect of the genotypes on body mass index (BMI), we performed a meta-analysis of the data from the literature using an extension of ANOVA for continuous measures. In a total of 48 subgroups containing subjects with (n = 2447) and without (n = 6789) the Trp⁶⁴Arg variant, the summary weighted mean difference in BMI was 0.30 (95% confidence interval, 0.13–0.47) kg/m², indicating that variant carriers exhibited higher BMI (on the average, 0.30 kg/m² higher) than normal homozygous subjects. In this case, there was no significant evidence against homogeneity of the effect (P = 0.36). This is the first meta-analysis assessing quantitative phenotypes in relation to a genetic polymorphism, and the results support the hypothesis that the Trp⁶⁴Arg polymorphism is associated with BMI across diverse population groups, suggesting that the ß₃-adrenergic receptor gene locus plays a role in genetic predisposition to increased body weight in a universal manner.

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