Premature Coronary Artery Disease; Association of IL-6 Receptor Gene Polymorphism ASP358ALA (A>CRS8192284) with Pro-Inflammatory Cytokines and Cytokine Mediator Serum Levels

Abstract

Objectives: Interleukin-6 receptor (IL-6R) gene (A>C, rs8192284) polymorphism has been associated with inflammatory biomarkers. We sought to investigate the association of IL-6R gene (A>C, rs8192284) polymorphism with IL-6, IL-18 and hS-CRP levels in PCAD. Study Design: Case control study. Setting: Army Medical College, National University of Sciences and Technology, Islamabad, Pakistan Methods: Total 520 subjects were recruited. 281 PCAD patients aged ≤45 years with >70% stenosis in at least one major coronary vessel along with 239 age and sex matched controls were recruited. IL-6R polymorphism was determined by TaqMan genotyping while IL-6 and IL-18 levels were measured using ELISA technique and hSCRP on Immulite 2000. Results: The genotype distribution of IL-6R(rs8192284) in the cases and controls was: AA-56%(n=143);AC-36% (n=102); and CC-13% (n=36) and AA-59%(n=139); AC-33% (n=80); CC-8% (n=20) respectively. The risk allele frequency was significantly different between the cases and controls (p=0.038) .IL-6 levels were significantly high (p<0.01) while hS-CRP levels were significantly low (p<0.05) in subjects with IL-6R (rs8192284) CC genotype as compared to the AC and AA genotypes. Multivariate logistic regression analysis revealed that IL-18, IL-6 and hS-CRP still remained significant in the prediction of PCAD with a high odds ratio OR (p<0.05). Conclusions: Our study is the first to show that the presence of the IL-6R rs8192284 is associated with significantly high IL-6 level and significantly low hS-CRP levels in Pakistani Premature Coronary Artery Disease Patients.