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Clinical features associated with the homozygous Trp64Arg mutation of the beta3-adrenergic receptor: no evidence for its association with obesity in Japanese.

To characterize the clinical features associated with the Trp64Arg mutation of the beta3-adrenergic receptor (beta3-AR), the effects of this mutation, in particular the homozygous state (Arg/Arg), on obesity, blood pressure, and plasma lipoproteins were investigated in 2 populations: subjects residing on a small isolated island (group 1; n=746) and patients residing in Tokyo who attend a clinic for metabolic diseases (group 2; n=371). The allelic frequency of the Trp64Arg mutation was 23.4% in group 1 and 18.3% in group 2. No significant difference in the body mass index was observed between subjects with 3 different genotypes in each group. There was a trend that the Arg/Arg had higher systolic blood pressure than the Trp/Trp in both groups, but the differences were not statistically significant. The plasma LDL cholesterol levels were significantly lower in Arg/Arg than in Trp/Trp in men from the group 1 cohort (2.82+/-0.84 versus 3.19+/-0.7 mmol/L, P<0.05). These results suggest that the homozygous Trp64Arg mutation is not a major contributing factor for obesity, but potentially contributed to higher systolic blood pressure and low plasma levels of LDL cholesterol in Japanese men.