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

J Med Biochem. 2015 Oct;34(4):402-408. doi: 10.2478/jomb-2014-0066. Epub 2015 Sep 19.

Abstract

Background: Oxidative 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.

Methods: The 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).

Results: There 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).

Conclusions: Our findings indicated that rs1049255 but not rs4673 polymorphism is associated with premature AMI.

Uvod: Oksidativni stres izazvan superoksidnim anjonom ima važne uloge u patogenezi koronarne arterijske bolesti (KAB) a time i akutnog infarkta miokarda (AIM). Glavni izvor produkcije superoksida u ćelijama vaskularnog glatkog mišića i endotelnim ćelijama je kompleks NADPH oksidaza. Važna komponenta ovog kompleksa je p22phox, koji kodira gen citohrom b-245, alfa polipeptid (CYBA). Cilj ove studije bio je da se ispita povezanost varijanti CYBA (rs1049255 i rs4673) sa rizikom od prevremenog akutnog infarkta miokarda u jednoj populaciji Iranaca.

Metode: Proučavanu populaciju činilo je 158 pacijenata mlađih od 50 godina sa dijagnozom prevremenog AIM, i 168 kontrolnih ispitanika odgovarajuće starosne dobi sa normalnim koronarnim angiogramima. Genotipizacija polimorfizama je obavljena pomoću reakcije lančane polimeraze i polimorfizma dužine restrikcionih fragmenata (PCR-RFLP).

Rezultati: Nije utvrđeno postojanje veze između genotipova i učestalosti alela polimorfizma rs4673 i prevremenog akutnog infarkta miokarda (P>0,05). Značajna statistička povezanost je uočena između distribucije genotipova polimorfizma rs1049255 i rizika od AIM (P=0,037). Štaviše, distribucija genotipova AA+AG/GG pokazala se kao statistički značajna između dve grupe (P=0,011).

Zaključak: Naši nalazi ukazuju na to da polimorfizam rs1049255 jeste, ali rs4673 nije povezan sa prevremenim AIM.

Keywords: acute myocardial infarction; p22phox; polymorphism; rs1049255; rs4673.