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The association of the Trp64Arg polymorphism of the beta3-adrenoceptor (beta3-AR) gene with high blood pressure, central adiposity and other features of the metabolic syndrome was investigated in a large unselected sample of a white male working population in Southern Italy (n = 979).In the whole population, subjects heterozygous for the Trp64Arg mutation (11.2%) were not different from the homozygous Trp64Trp for any of the variables investigated. However, upon stratification for age, among men in the upper tertile of age (> 53 years), the Trp64Arg genotype was associated with higher waist : hip ratio (0.992 ± 0.021 versus 0.982 ± 0.037, P< 0.05), serum uric acid (6.34 ± 1.50 versus 5.75 ± 1.30 μmol/l, P< 0.05) and systolic blood pressure (144.3 ± 19.4 versus 136.9 ± 18.9 mmHg, P< 0.05) compared with the wild-type homozygotes. Accordingly, in the same age group, the carriers of Trp64Arg genotype were more often in the upper tertile of abdominal adiposity (69.7 versus 43.7%, P< 0.02) and serum uric acid (56.3 versus 34.8%, P< 0.02) and were more often hypertensive (68.6 versus 57.6%, P< 0.058) than the Trp64Trp homozygotes. No such differences were observed in younger age groups. No association was found with fasting serum insulin and the homeostasis model assessment (HOMA) index of insulin resistance. Furthermore, in a subgroup of 457 men for whom retrospective 20-year follow-up data were available, the variant genotype was associated with a higher probability of developing overweight (44.7 versus 27.0%, P< 0.05) and a trend to higher blood pressure (52.6 versus 38.4%, P = 0.09) over 20 years.We conclude that the Trp64Arg variant of the beta3-AR receptor predicts a greater tendency to develop abdominal adiposity and high blood pressure with advancing age.