Recently, we reported that the polymorphism 1132T>C (GenBank: AF519768.1) of the NOS3 gene was associated with susceptibility to metabolic syndrome (MS) in hypertensive patients. This suggests that other genes such as CAV1, whose product (CAV1) regulates eNOS activity, could also be related to this phenotype. In this work we investigated the following: i) whether CAV1 is a quantitative trait locus of clustering of atherothrombotic traits associated with MS; ii) whether CVA1 is associated with hypertension or MS in hypertensive patients; and iii) whether genetic interaction between NOS3 and CAV1 is involved in the susceptibility or protection to hypertension associated with MS. To carry out the study, we genotyped 285 randomly selected individuals and 175 hypertensive patients, all of them < or = 60 years old, with two polymorphisms of the CAV1 gene: the 22285 C>T and the 22375-22375 del AC (GenBank AF125348), and the 1132T>C polymorphism of the NOS3 gene. To perform sample genotyping, we used pyrosequencing and FRET techniques. The 22285 C-22375-22375 del (Cd) haplotype of CAV1 gene was associated with low levels of blood pressure in the general population. Moreover, it was a genetic protection factor against MS in hypertensive patients. In addition, we found no evidence of gene-gene interaction between NOS3 and CAV1 genes with regard to that phenotype.