BACKGROUND: The -344C/T variant in the promoter of the aldosterone synthase gene (CYP11B2) has been associated with hypertension and may influence glucose homeostasis and body mass in humans. We assessed the association between this genetic variant and metabolic syndrome in a large sample of European population. METHODS: Eight hundred two male/female couples, recruited in the framework of the IMMIDIET study, a survey on cardiovascular risk in Italy, UK, and Belgium, had standardized measurements of body mass index, waist circumference, blood pressure (BP), serum total and HDL-cholesterol, triglycerides, and glucose and were genotyped for the -344C/T variant of CYP11B2. Metabolic syndrome was defined according to the International Diabetes Federation criteria. RESULTS: The prevalence of the metabolic syndrome was 23.9% in men and 14.0% in women. The C allele of the variant was associated with metabolic syndrome in men (P = .002) but not in women. At logistic regression analysis, the odds ratio of metabolic syndrome increased progressively with the number of copies of the C allele (CT: 1.54, 95% CI from 1.01 to 2.35; CC: 2.25, 95% CI from 1.38 to 3.66) as compared with the TT homozygotes, taken as reference genotype. CONCLUSIONS: The C allele of -344C/T variant of CYP11B2 increases susceptibility to metabolic syndrome in European men, but not in women, suggesting a pleiotropic role for this gene in modulating cardiovascular risk.