Endogenous catecholamines contribute to regulation of adipose tissue lipolysis, glucose homeostasis, and vascular tone. The goal of the present study was to assess the association between the Gly(16)-->Arg(16) and Gln(27)-->Glu(27) polymorphisms of the beta(2)-adrenergic receptor and metabolic syndrome. Participants were recruited in a population survey and included 1195 men and women. Metabolic syndrome was defined according to National Cholesterol Education Program Adult Treatment Panel III guidelines. There were 276 patients with metabolic syndrome and 872 controls. The Gly(16)-->Arg(16) (P < 0.005) and Gln(27)-->Glu(27) (P < 0.04) polymorphisms were associated with metabolic syndrome in men, but not in women. In multivariate analyses adjusting for age, physical activity, smoking habits, alcohol consumption, and body mass index, the odds ratio of metabolic syndrome was 1.83 (95% confidence interval, 1.10-3.05) and 2.43 (95% confidence interval, 1.19-4.95) in men bearing the Gly(16)/Arg(16) and Arg(16)/Arg(16) genotypes, respectively. Similarly, the odds ratios of metabolic syndrome were 0.99 (95% confidence interval, 0.50-1.93) and 1.67 (95% confidence interval, 0.84-3.33) in men bearing the Gln(27)/Glu(27) and Gln(27)/Gln(27) genotypes, respectively. Because both variants were in linkage disequilibrium, a haplotype analysis was performed. There was no evidence of any statistically significant association between beta(2)-adrenergic receptor haplotypes and metabolic syndrome. In conclusion, these data suggest that the Arg(16) and Gln(27) variants of the beta(2)-adrenergic receptor gene contribute to metabolic syndrome susceptibility in men.