Contribution of a missense mutation (Trp64Arg) in beta 3-adrenergic receptor gene to multiple risk factors in Japanese men with hyperuricemia

Epidemiological data reveal that hyperuricemia is a risk factor of atherosc lerosis. The risk is possibly caused by a link between hyperuricemia and in sulin resistance-related metabolic syndrome. Recently it has been proposed that a missense mutation (Trp64Arg) in the beta 3-adrenergic receptor (beta 3-AR) gene may contribute to the accumulation of multiple risk factors rel ated to insulin resistance. The present study was undertaken to further cla rify an association between the Trp64Arg mutation and the metabolic syndrom e in 47 Japanese men with hyperuricemia, who are substantially at high risk of atherosclerosis. One patient (2%) had the homozygous mutation, 12 (26%) were heterozygous for the mutation, and 31 (72%) had no mutation found by the PCR-RFLP analysis. The Trp64Arg mutation was not related to past maxima l body mass index (BMI), BMI and waist/hip ratio. The subjects with the het erozygous mutation showed a slightly higher incidence of impaired glucose t olerance and diabetes mellitus in the 75 g oral glucose challenge (67%), as compared with those without the mutation (39%). Serum insulin response at 60 min and the sum of serum insulin in the glucose challenge were greater i n the former subjects than those in the latter subjects (P=0.041 and 0.076, respectively). An increase in serum lipoprotein(a) was also observed in th e subjects with the heterozygous mutation, but the Trp64Arg mutation was no t associated with other dyslipidemia, blood pressure or ischemic changes on the electrocardiogram. These results indicate that the heterozygous mutati on of Trp64Arg in the beta 3-AR gene partly contributes to the accumulation of multiple risk factors in male subjects with hyperuricemia. A larger pro spective study is necessary to elucidate a possible role of the Trp64Arg mu tation in atherosclerotic diseases in future.