Meta‐Analysis of the Association of the Trp64Arg Polymorphism in the β3 Adrenergic Receptor with Insulin Resistance

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To clarify the possible association between the Trp64Arg polymorphism and insulin resistance (IR). Articles evaluating the effect of the Trp64Arg polymorphism on IR were identified on the MEDLINE and PubMed databases from 1995 to February, 2004. After extraction of relevant data, main and subgroup meta-analyses were performed to assess the differences in IR indices between Trp/Trp and Trp/Arg genotypes. Forty eligible papers containing 56 subgroups were included in this meta-analysis. Among a total of 12,805 subjects, 21.9% had Trp64Arg mutation: 20.8%, heterozygotes and 1.1%, homozygotes. Significant associations were found between this mutation and some indices of IR. The weighted mean difference in fasting insulin, 120-minute insulin level after oral glucose tolerance test, and homeostasis model assessment between Arg64 and Trp64 was 0.23 [95% confidence interval (CI), 0.05 to 0.42] pM, 0.89 (95% CI, 0.30 to 1.48) pM, and 0.55 (95% CI, 0.14 to 0.96), respectively. Subgroup analysis further indicated that this significant association existed only in the Asian population (p < 0.01) and in the obese (p = 0.02) and diabetes subgroups (p = 0.03). Numerous studies have been conducted to examine the relationship between the beta3-adrenergic receptor Trp64Arg polymorphism and components of IR syndrome. However, the results have been inconsistent and have led to controversy about whether this polymorphism is associated with these clinical features. The current meta-analysis demonstrated the moderate effects of the Trp64Arg polymorphism on IR in the Asian population and in obese and diabetic subgroups.