Genetic diversity of RANTES gene promoter and susceptibility to coronary artery disease and restenosis after percutaneous coronary intervention

Abstract

Regulated on activation, normal T cell expressed and secreted (RANTES) gene promoter is a regulatory region and a site of notable genetic diversity. In order to explore a possible interaction between RANTES promoter genetic diversity and susceptibility to coronary artery disease (CAD) and in stent restenosis (ISR), we initially sequenced a locus extending from -516 to 40 covering the entire region of the RANTES promoter in 100 subjects randomly selected from our cohort. Four single nucleotide polymorphisms (SNPs) were identified: -403G/A, -256G/A, -109C/T and -28C/G. The frequency of the -109C/T and -256G/A variations was <0.01, and was considered to be of limited significance. The frequency of the -403G/A and -28C/G polymorphisms was evaluated in the entire sample, which consisted of 118 patients subjected to percutaneous coronary intervention (PCI) without ISR on angiographic re-evaluation (no IRS group), 74 CAD patients with ISR on angiographic re-evaluation (IRS group) and 146 controls without angiographic evidence of CAD (no CAD group). No association was established between the RANTES promoter genotype and ISR. A genotype-phenotype interaction was observed between the -403G/A polymorphism and CAD. The -403A homozygotes were significantly more common in the CAD group than in the controls. The severity of CAD among case subjects, expressed as the mean number of diseased vessels, was significantly higher among -403A homozygotes as compared to wild-type homozygotes and heterozygotes. In conclusion, the RANTES -403A allele was associated with the presence and severity of CAD independently of conventional cardiovascular risk factors. The RANTES promoter genotype did not influence susceptibility to ISR in patients subjected to PCI.