Genetic Variants of Cytochrome b-245, Alpha Polypeptide Gene and Premature Acute Myocardial Infarction Risk in an Iranian Population.

Fatemeh Amin,Hamid Ghaedi,Zohreh Sharifi,Kazem Mousavizadeh,Asaad Azarnejad,Mohammad Mehdi Jahani,Aliasghar Valipour,Michael Tajik,Mohammad Askari,Taghi Golmohammadi,Sadegh Alipoor,Behnam Alipoor,Ahmad Fatemi

doi:10.2478/jomb-2014-0066

Abstract

SummaryBackgroundOxidative stress induced by superoxide anion plays critical roles in the pathogenesis of coronary artery disease (CAD) and hence acute myocardial infarction (AMI). The major source of superoxide production in vascular smooth muscle and endothelial cells is the NADPH oxidase complex. An essential component of this complex is p22phox, that is encoded by the cytochrome b-245, alpha polypeptide (CYBA) gene. The aim of this study was to investigate the association of CYBA variants (rs1049255 and rs4673) and premature acute myocardial infarction risk in an Iranian population.MethodsThe study population consisted of 158 patients under the age of 50 years, with a diagnosis of premature AMI, and 168 age-matched controls with normal coronary angiograms. Genotyping of the polymorphisms was performed by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP).ResultsThere was no association between the genotypes and allele frequencies of rs4673 polymorphism and premature acute myocardial infarction (P>0.05). A significant statistical association was observed between the genotypes distribution of rs1049255 polymorphism and AMI risk (P=0.037). Furthermore, the distribution of AA+AG/GG genotypes was found to be statistically significant between the two groups (P=0.011).ConclusionsOur findings indicated that rs1049255 but not rs4673 polymorphism is associated with premature AMI.

Highlights

Acute myocardial infarction (AMI) is one of the leading causes of morbidity and mortality in the world
Our findings indicated that rs1049255 but not rs4673 polymorphism is associated with premature AMI
All Nox appear to have an essential requirement for p22phox which is a heme binding protein that is located in the membrane. p22phox is composed of the a subunit of cytochrome b-245 and acts as an electron transfer element of Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase

Summary

Introduction

Acute myocardial infarction (AMI) is one of the leading causes of morbidity and mortality in the world. The primary function of these enzymes is the production of reactive oxygen species (ROSs) such as superoxide anion (O2) in many cells endothelial and vascular smooth cells [4, 5]. Coupling components such as p22phox, p47phox, p67phox, p40phox and Rac are necessary for the activity and stabilization of these isoforms. P22phox is composed of the a subunit of cytochrome b-245 and acts as an electron transfer element of NADPH oxidase This subunit is encoded by the CYBA gene that is located on chromosome 16q24 and spans 8.5 kb (6 exons and 5 introns) [6]

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