The NLRP3 and CASP1 gene polymorphisms are associated with developing of acute coronary syndrome: a case-control study.

Abstract

The protein products of NLRP3 and CASP1 genes are involved in the cleavage of pro-IL-1B and pro-IL-18 leading to the active cytokines, which play an important role in the development of the acute coronary syndrome (ACS). The aim of the present study was to evaluate whether NLRP3 and CASP1 gene polymorphisms are biomarkers of ACS susceptibility in Mexican population. Two polymorphisms of the CASP1 gene [G+7/in6A (rs501192) and A10370-G Exon-6 (rs580253)] and one of the NLRP3 gene [UTR'3 G37562-C (rs10754558)] were genotyped by 5' exonuclease TaqMan assays in a group of 617 patients with ACS and 609 control individuals. Under recessive model, the CASP1 G+7/in6A polymorphism was associated with an increased risk of developing ACS when compared to healthy controls (OR=1.76, 95% CI 1.08-2.86, P Res =0.022). In the same way, under recessive model, the CASP1 A10370-G was associated with increased risk of ACS (OR=1.75, 95% CI 1.07-2.85, P Res =0.025). Moreover, under co-dominant, dominant, over-dominant, and additive models, the NLRP3 UTR'3 G37562-C was associated with a decreased risk of ACS (OR=0.45, 95%CI 0.22-0.92, P Co-dom =0.006; OR=0.61, 95%CI 0.44-0.84, P Dom =0.002; OR=0.67, 95%CI 0.48-0.94, P Over-dom =0.02; and OR=0.65, 95%CI 0.50-0.94, P Add =0.02, respectively). In summary, this study demonstrates that the G+7/in6A and A10370-G polymorphisms of the CASP1 gene are associated with increased risk of developing ACS, whereas the UTR'3 G37562-C polymorphism of the NLRP3 gene is associated with a decreased risk of developing ACS in Mexican population.