Analysis of selected promoter polymorphisms and haplotypes of the CYBA gene encoding the p22phox, subunit of NADPH oxidases, in patients with coronary artery disease

The p22phox is a critical component of vascular NADPH oxidases and is encoded by the CYBA gene. It was shown that functionally relevant polymorphisms of the CYBA gene -930A>G, -852C>G, -675A>T, -536C>T, 214C>T (previously described as 242C>T), *24A>G (previously described as 640A>G), and *49A>G modulate generation of reactive oxygen species (ROS). To analyse whether the CYBA gene polymorphisms -852C>G, -675A>T, and -536C>T were associated with coronary artery disease (CAD), and to designate haplotype blocks. Four hundred and ninety subjects: 245 patients with CAD and 245 age and sex-matched controls. The polymorphisms were genotyped using the PCR-RFLP method and the TagMan (R) Pre-designed SNP Genotyping Assay. The analysed polymorphisms do not form haplotype blocks. Case-control study revealed that the -930G/-675T and -930G/*49G diplotypes were a CAD risk factor. The 675T/*49G diplotype can modulate CAD risk in women. The protective effect reducing CAD risk in women was related to the -930A/-675T and -930A/*49A diplotypes. Carrier state of the -852C allele (-852C>G) was associated with multivessel stenosis while the CC genotype of the -536C>T polymorphism was more frequent in patients with peripheral artery disease. Hypercholesterolemic, cigarette smokers had an increased risk of CAD, especially C-852 allele (-852C>G) carriers (SIM = 3.54; odds ratios (OR) = 10.01, p < 0.000). The CYBA gene polymorphisms modulate the risk of CAD but do not form a haplotype blocks.