The SNP rs7865618 of 9p21.3 locus emerges as the most promising marker of coronary artery disease in the southern Indian population

Gorre Manjula,Rayabarapu Pranavchand,Irgam Kumuda,B Sriteja Reddy,Battini Mohan Reddy

doi:10.1038/s41598-020-77080-4

Abstract

Development of coronary artery disease (CAD) is primarily due to the process of atherosclerosis, however the prognosis of CAD depends on pleiotropic effects of the genes located at 9p21.3 region. Genome wide association studies revealed association of variants in this region with CAD pathology. However, specific marker in predicting CAD development or progression is not yet identified. In the present study, 35 SNPs at 9p21.3 region, located in the cyclin dependent kinase inhibitor (CDKN2A/CDKN2B) genes, were genotyped among 350 CAD cases and 480 controls from the southern Indian population of Hyderabad using fluidigm nanofluidic SNP genotyping system and the data were analyzed using PLINK and R softwares. Of the 35 SNPs analysed, only one SNP, rs7865618, was found to be highly significantly associated with CAD, even after correction for multiple testing (p = 0.008). The AG and GG genotypes of this SNP conferred 3.08 and 1.93 folds increased risk for CAD respectively. In particular, this SNP was significantly associated with severe anatomic (triple vessel disease p = 0.023) and phenotypic (acute coronary syndrome p = 0.007) categories of CAD. Pair wise SNP interaction analysis between the SNPs of 9p21.3 and 11q23.3 regions revealed significantly increased risk of three SNPs of 11q23.3 region that were not associated individually, in conjunction with rs7865618 of 9p21.3.

Highlights

Development of coronary artery disease (CAD) is primarily due to the process of atherosclerosis, the prognosis of CAD depends on pleiotropic effects of the genes located at 9p21.3 region
The complex nature of CAD phenotype might be the outcome of interactions of different genomic loci
Since the SNPs at 11q23.3 region harbouring apolipoprotein coding genes namely APOA1, APOC3, APOA4, APOA5 and regulatory genes BUD13, ZPR1, SIK3 were found to be associated with defective lipid metabolism, this region was thought to play an important role in atherosclerosis and CAD risk

Summary

Introduction

Development of coronary artery disease (CAD) is primarily due to the process of atherosclerosis, the prognosis of CAD depends on pleiotropic effects of the genes located at 9p21.3 region. The present study deals with a comprehensive set of 35 GWAS identified SNPs at the 9p21.3 chromosomal region for their possible association with risk for CAD and its anatomical and phenotypic sub-categories, either individually or through their interactions with other SNPs in the same region as well as with those of the 11q23.3 region.

Results

Conclusion