|
Abstract
|
Background The p22phox gene encodes the main subunit of NADH/NADPH-oxidase. This enzyme is expressed in smooth muscle cells of arteries, and it produces the reactive oxygen species. On the other hand, oxidative stress plays a main role in the pathogenesis of coronary artery disease (CAD). Aim The aim of this study is to evaluate the association between rs4673 and rs1049255 polymorphisms of p22phox gene with CAD in an Iranian population which was followed with a computational analysis approach. Methods In a cross-sectional study, we collected blood samples of 302 Iranian Caucasian including 143 patients and 159 healthy controls. Genotype of the polymorphisms was detectedthroughPCR-RFLPmethod.Acomputationalanalysiswas also performed using SNAP, Polyphen-2, Chou-Fasman, RNAsnp, and miRNA SNP databases. Results Data of case control study demonstrated that CT genotype(R=1.84,95%CI=1.13–3.00,p=0.014)andTallele (OR = 1.53, 95% CI = 1.09–2.15, p = 0.013) of rs4673 polymorphism, have a significant association with enhanced risk ofCAD. Butrs1049255analysisdemonstratedthe absence of such an association with CAD. Indeed, in silico data analysis demonstrated that rs4673 transition could impact on function of p22phox protein (SNAP score 56, expectedaccuracy75%; Polyphen-2score0.99,sensitivity0.09,specificity0.99).Data derived from miRNA SNP database demonstrated that rs1049255 polymorphism increases the affinity of attachment between has-miR-3689a-3b with 3′-UTR of p22phox gene. Conclusion Ourdatademonstratedthatrs4673transitionmay beinvolvedinsusceptibilitytoCADandcouldbeappliedasa potential biomarker for this disease.
|