ABSTRACT
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.
Subject(s)
Caveolin 1/genetics , Genetic Predisposition to Disease , Hypertension/genetics , Metabolic Syndrome/genetics , Nitric Oxide Synthase Type III/metabolism , Polymorphism, Genetic , Case-Control Studies , Fluorescence Resonance Energy Transfer , Humans , Models, Genetic , Polymorphism, Single Nucleotide , Quantitative Trait Loci , Sequence Analysis, DNA , Thrombosis/geneticsABSTRACT
Recent data from animal models indicate that the eNOS null mice present a phenotype that resemble the human metabolic syndrome (hypertension, insulin resistance and hypertriglyceridemia). In this work, we have studied whether NOS3 gene, previously related to endothelial dysfunction, might have a role in metabolic syndrome susceptibility in hypertensive patients. To carry out the study, we genotyped 105 hypertensive patients < or = 60 years old with two polymorphisms of NOS3 gene: 1132 T>C and 7164 G>T (GeneBank:AF519768.1). To check the allelic frequency of these polymorphisms in our geographical area, we also genotyped 94 unselected healthy controls (control group). To perform sample genotyping, we designed a novel FRET system coupled to real time PCR. There were no differences in genotypic distribution or allelic frequency between hypertensive patients and the control group. However, we observed that 786CC genotype was significantly more frequent in hypertensive patients with metabolic syndrome than in those without the syndrome (p=0.0022). When both polymorphisms were analyzed, we identified the 786C894G as the risk haplotype for metabolic syndrome susceptibility (p=0.011). These data suggest a role of the NOS3 gene in the pathogenesis of metabolic syndrome in hypertensive patients.
