Meta-analysis of the association of the Trp64Arg polymorphism in the β₃ adrenergic receptor with body mass index

OBJECTIVE: As a result of efforts to isolate obesity-promoting genes, the Trp64Arg polymorphism in the β₃ adrenergic receptor locus, has been studied by many investigators. Results of the studies have varied in statistical significance and magnitude of the association of the polymorphism with body mass index (BMI: kg/m²). This has led to controversy about whether this polymorphism is associated with meaningful changes in BMI. To clarify the possible association, we conducted a meta-analysis. DESIGN: Meta-analytic study. MEASUREMENTS: For each genotype of the β₃ adrenergic receptor (Trp/Trp; Trp/Arg; Arg/Arg), we extracted the number of subjects, mean and standard deviation of BMI from 23 studies, including 36 different subgroups with a total of 7399 subjects. Other indices and obesity-related variables were not considered. RESULTS: No significant association of the Trp64Arg polymorphism with BMI was found. The weighted mean BMI difference beween Trp/Trp homozygotes and Trp/Arg heterozygotes was 0.19 (s.e. = 0.11; P = 0.07). In addition, the distribution of effect sizes was not significantly heterogeneous (χ² = 38.68; df 35; P = 0.31) suggesting that the variation of the effect sizes across the subgroups is not significant. A further weighted regression analysis, utilizing all three genotypes and adjusting for the random subgroup effect, also showed the effect of the polymorphism on BMI is not significant (F = 1.72, df = (2,54), P = 0.19). CONCLUSION: Based on existing data, the Trp64Arg polymorphism does not appear to be significantly associated with BMI. Moreover, we found no evidence for effect heterogeneity, suggesting that the effect of the polymorphism is not moderated by ethnicity or diabetic status.