The -174 G>C Interleukin-6 Gene Polymorphism is Associated with Angiographic Progression of Coronary Artery Disease over a 4-Year Period

Abstract

Background: Inflammation is a key process underlying the clinical course of coronary artery disease (CAD). C-reactive protein (CRP) and interleukin-6 (IL-6) contribute to its pathophysiology and act as biomarkers. We sought to examine whether known single nucleotide polymorphisms (SNPs) impact CAD progression, reflecting increased inflammation. Methods: We retrospectively evaluated coronary angiographies of patients with established CAD who were re-investigated for stable/unstable angina after a time interval of >12 months. We defined progression of CAD as the emergence of a new plaque or a ≥20 % increase of a formerly non-significant lesion. We genotyped patients for the 1846 C>T CRP and -174 G>C IL-6 SNPs. The probability of CAD progression among the Mendelian randomization groups was evaluated using the Kaplan–Meier method. Data were analyzed using a Cox model that included relevant clinical factors. Results: A total of 157 patients were included. The serum levels of CRP and IL-6 differed significantly between genotypes. The genotype frequencies of IL-6 were consistent with Hardy–Weinberg equilibrium, whereas those for CRP were excluded from our conclusions. At 48 months, 83 patients (52.9 %) with the IL-6 C allele versus 74 (47.1 %) with the G allele exhibited CAD progression. Patients with the IL-6 C allele had a 52.8 % probability for progression versus 13.3 % for those with the G allele (p=0.005). The results were confirmed by multivariate analysis; dyslipidemia, family history, and IL-6 SNP emerged as significant factors. Conclusion: Patients with established CAD who carried the -174 C allele of the IL-6 gene demonstrated an increased risk for the progression of coronary plaques over a four-year period. Further studies will be needed to validate these findings. Keywords: Coronary artery disease, inflammation, progression, interleukin-6, gene polymorphisms, SNP