Role of Cytokine Gene Score in Risk Prediction of Premature Coronary Artery Disease

Abstract

Aims: Pro- and anti-inflammatory cytokines play a significant role in early atherosclerosis. Linkage disequilibrium patterns differ between ethnic groups pointing toward the need to develop population-specific gene risk scores. Our objective was to investigate the role of a cytokine gene score in the risk prediction of premature coronary artery disease (PCAD). Methods: A case-control study was performed at the National University of Sciences and Technology (NUST) in collaboration with the Cardiovascular Genetics Institute, University College London, United Kingdom. Three hundred forty subjects with >70% stenosis in at least one coronary vessel on angiography were labeled as PCAD cases and compared with 310 angio-negative controls. Genotyping of the rs187238 (interleukin [IL]-18), rs1800795 (IL-6), rs1800629 (tumor necrosis factor [TNF]-alpha), rs1800871 (IL-10), and rs1946519 (IL-18) SNPs was performed using KASPar and TaqMan assays. Results: The odds ratio for cytokine gene score was significantly higher for PCAD (p = 0.025) when adjusted for age, sex, and ethnicity. There was a highly significant difference in gene risk allele frequency between Pakistanis and Caucasians (Northwick Park Heart Study II [NPHSII]) for rs187238 (IL-18), rs1800795 (IL-6), rs1800629 (TNF-alpha), and rs1800871 (IL-10) (p < 0.01). Conclusions: A cytokine gene score has significant discriminatory ability and potential in the risk prediction of PCAD. Cytokine gene risk allele frequencies differ significantly between Pakistanis and Caucasians supporting the need to develop population-specific gene scores.