Association of IL-8-251 A/T rs4073 and IL-10 rs1800872 -592C/A Polymorphisms and Coronary Artery Disease in North Indian Population.

CAD (Coronary Artery Disease) morbidity is becoming an endemic worldwide. Recently, the role of pro- and anti-inflammatory cytokines in the development of atherosclerotic plaques has been explored, but the association of their genetic polymorphisms and CAD has yet not been established. The present study aimed to investigate the association of IL-8-251A/T (rs4073) and IL-10 -592C/A (rs1800872) polymorphisms and the risk of CAD in North Indian population. 1000 subjects (500 angiographically confirmed CAD patients and 500 controls) were genotyped by ARMS-PCR. Results revealed a significant risk association of both the polymorphisms with CAD. The heterozygous and the mutant genotypes of IL-8 rs4073 were both found to be associated with the risk of disease after adjusting for the confounders (padj  < 0.001, ORadj 3.121, 95% CI 1.926-5.056 and padj  < 0.001, ORadj 3.116, 95% CI 1.952-4.973, respectively), but only the mutant AA genotype of IL-10 rs1800872 correlated with risk of disease with padj  < 0.001, ORadj 4.106, 95% CI 2.160-7.806). Stratifying the samples on the basis of gender revealed CAD in heterozygous and mutant in males (padj  < 0.001, ORadj 3.693, 95% CI 2.031-6.716; padj  < 0.001, ORadj 3.288, 95% CI 1.848-5.851, respectively) and only the mutant to be associated with risk of disease in females (padj  = 0.010, ORadj 2.867, 95% CI 1.284-6.404) for IL-8 rs4073, whereas only the mutant genotype AA of IL-10 rs1800872 associated with CAD risk in males (padj  < 0.001, ORadj 5.821, 95% CI 2.831-11.970). Stratified analysis based on age showed a significant higher risk in the heterozygous and mutant genotype in subjects below 40 years of age (padj  = 0.039, ORadj 5.052, 95% CI 1.081-23.602; and padj  = 0.025, ORadj 5.533, 95% CI 1.239-24.704, respectively) compared with the heterozygous and mutant genotype association of the risk of disease in subjects above 40 years of age (padj  < 0.000, ORadj 2.964, 95% CI 1.747-5.027; and padj  < 0.000, ORadj 2.859, 95% CI 1.716-4.762, respectively) in IL-8 rs4073. For IL-10 rs1800872, risk association was seen only in subjects above 40 years of age (padj  < 0.001, ORadj 5.049, and 95% CI 2.414-10.561). The present study exhibited associations of IL-8-251A/T (rs4073) and IL-10 -592C/A (rs1800872) with CAD in the North Indian population and also that the associations are gender and age dependent.