Association of angiotensin-converting enzyme, methylene tetrahydrofolate reductase and paraoxonase gene polymorphism and coronary artery disease in an Indian population.

BACKGROUND Coronary artery disease (CAD) and cancer remain the leading causes of death in most developed countries. Elucidating the genetic components that contribute to their pathogenesis is challenging. In this case-control association study, we examine the association of single nucleotide polymorphisms (SNPs) in paraoxonase 573 A/G genes, methylene tetrahydrofolate reductase (MTHFR) 677 C/T and angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with CAD independently, as well as synergistically, in a north Indian population. METHODS AND RESULTS Patients with at least 50% stenosis of at least one major coronary artery were classified as cases. The controls had no myocardial infarction. Polymerase chain reactions (PCR) followed by restriction fragment length polymorphism (RFLP) analyses were carried out to determine the SNPs. No significant association of the polymorphisms of the ACE or MTHFR genes with the risk of CAD was observed. However, the allele frequencies of the 573 A/G polymorphism of the paraoxonase gene differed significantly among cases and controls before and after controlling for confounding factors. The frequencies of AG vs AA genotypes and GG+AG vs AA genotypes also differed significantly in the two groups (p = 0.0002). The interaction of paraoxanase with both MTHFR and ACE independently showed significant positive associations. CONCLUSIONS The identification of 'at risk' individuals by genetic mapping of susceptible genes for effective control of other host factors will be a very effective and practical approach for prevention, as well as the development of improved therapy for patients.