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

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.