PREMATURE CORONARY ARTERY DISEASE

ASSOCIATION OF IL-6 RECEPTOR GENE POLYMORPHISM ASP358ALA (A>C RS8192284) WITH PRO-INFLAMMATORY CYTOKINES AND CYTOKINE MEDIATOR SERUM LEVELS wafamuniransari@yahoo.

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.