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

BACKGROUND: 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).

AIM: 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.

METHODS: 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® Pre-designed SNP Genotyping Assay.

RESULTS: The analysed polymorphisms do not form haplotype blocks. Case-control study revealed that the -930 G/-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).

CONCLUSIONS: The CYBA gene polymorphisms modulate the risk of CAD but do not form a haplotype blocks.