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Association Analysis of Rs1049255 and Rs4673 Transitions in P22phox Gene With Coronary Artery Disease: A Case-Control Study and a Computational Analysis Publisher Pubmed



Mazaheri M1 ; Karimian M2, 3 ; Behjati M1 ; Raygan F4 ; Hosseinzadeh Colagar A3
Authors
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Authors Affiliations
  1. 1. Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2. Anatomical Sciences Research Center, Kashan University of Medical Sciences, Kashan, Iran
  3. 3. Department of Molecular and Cell Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar, Iran
  4. 4. Department of Cardiology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran

Source: Irish Journal of Medical Science Published:2017


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 detected through PCR-RFLP method. A computational analysis was 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) and T allele (OR = 1.53, 95% CI = 1.09–2.15, p = 0.013) of rs4673 polymorphism, have a significant association with enhanced risk of CAD. But rs1049255 analysis demonstrated the 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, expected accuracy 75%; Polyphen-2 score 0.99, sensitivity 0.09, specificity 0.99). 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: Our data demonstrated that rs4673 transition may be involved in susceptibility to CAD and could be applied as a potential biomarker for this disease. © 2017, Royal Academy of Medicine in Ireland.
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