Association of CnB 5I/5D promoter gene polymorphism and serum calcineurin levels in early onset of coronary artery disease of south Indian cohort

Calcineurin, a serine/threonine phosphatase is a calcium dependent protein which on activation triggers transcriptional up regulation of inflammatory genes associated with inflammation in the arteries and progressive formation of plaques in CAD. The present investigation is aimed to study the possible association of Calcineurin encoding gene PPP3R1 (CnB 5I/5D) polymorphism in correlation with serum levels of calcineurin in coronary artery disease (CAD). A total of 300 angiographically documented CAD patients and 300 age, gender ethnicity matched healthy controls were recruited for the study. Serum Calcineurin levels were estimated by enzyme-linked immunosorbent assay (ELISA) and genotypes were determined based on PCR-RFLP. The CnB 5I/5D variation was found to be significantly associated with CAD (p < 0.03), correlated to elevated serum calcineurin levels encoded by (< 0.01) 5I/5D allele authenticated by Insilco analysis. Multiple logistic regression analysis also confirmed these findings [adjusted OR for DD genotype was 3.19 (95% CI 1.40-7.24) and p = 0.001]. The results suggest that 5-base pair deletion results in increased serum calcineurin levels and may trigger up regulation of calcineurin which mediates vascular inflammation and atherosclerosis in CAD.