Polymorphic variants of Caspase genes (8 & 3) in the risk prediction of Coronary Artery Disease

Abstract Apoptosis has been involved in a number of pathological conditions including coronary artery disease (CAD). Caspases (CASP) are important regulators and executioners in both extrinsic and intrinsic apoptotic pathways. The aim of the present study is to examine the role of Caspase 8 and 3 polymorphisms in the pathogenesis of CAD. CAD patients (n=300) and healthy controls (n=300) were genotyped for polymorphisms in CASP8 (−652 6N del/ins, IVS12-19G>A), CASP3 (rs4647601;G>T) by PCR-RFLP. Splicing defects were determined by HSF. Gene interactions, Linkage disequilibrium and haplotype analysis were carried out by MDR analysis and Haploview software respectively. Molecular analysis revealed that insertion genotype (II) of CASP8 −652 6N del/ins and TT genotype of CASP3 rs4647601;G>T polymorphism conferred risk for the development of CAD. HSF analysis showed that intronic cryptic donor site for CASP8 -652 6N del/ins and a new ESE site for CASP3 rs4647601;G>T polymorphisms. SNP combinations of Caspase 8 and 3 were in perfect LD (D′=1) in controls. D-A, I-G haplotypes of Caspase 8 polymorphisms (−652 6N del/ins & IVS12-19G>A) were found to be significantly predominant in the disease group. The present study suggests that CASP8 & 3 polymorphic variants might be used as markers for susceptibility to CAD.