9p21.3 coronary artery disease risk locus and interferon alpha 21: Association study in an Asian Indian population

Introduction: Type I Interferons (INFαs and INF β) are known to be proinflammatory cytokines that promote atherosclerosis. IFNA21 is a member of alpha Interferon gene cluster on short arm of chromosome 9. We analyzed the potential link between 9p21 coronary artery disease (CAD) risk locus and IFNA21.

Objectives: a) study of association between serum IFNA21 levels and 14 demographic/clinical variables, including age, gender, diabetes, hypertension, and duration of CAD, b) study of association between high serum IFNA21 levels and 30 9p21 SNP genotypes.

Methods: To estimate serum circulating levels of IFNA21, we performed sandwich ELISA in 184 controls and 167 CAD cases. The IFNA21 levels could be classified into two broad classes: a) Low-level group: ≤15.6 pg/ml b) High-level group: >15.6 pg/ml. We also performed SNP genotyping for 30 SNPs at 9p21 locus in all study subjects using Sequenom MassARRAY technology. Statistical software SPSS (Version 21) was used to analyze the data obtained.

Results: Our analysis indicates that there could be an association of high IFNA21 levels with variables - gender, age, and duration of CAD in the study population. SNPs rs10757272 (TT), rs10757274 (GG), rs10757283 (TT), rs1333045 (CC), rs1333048 (CC), rs1333049 (CC), and rs4977574 (GG) showed significant risk association with high-level IFNA21 group.

Conclusions: IFNA21 may be involved in inflammatory processes in an age-dependent manner and in progression of CAD. This IFNA21-mediated mechanism may be more active in females. Several 9p21 SNPs may modulate inflammatory processes mediated by IFNA21 and may, therefore, contribute to pathophysiology of CAD.