C242T Polymorphism in CYBA Gene (p22^phox) and Risk of Coronary Artery Disease in a Population of Caucasian Italians

Abstract

Background: specific polymorphisms of genes regulating intracellular redox balance and oxidative stress are related to atherogenesis. Some studies have identified a relationship between progression of atherosclerosis and C242T mutation in CYBA gene coding for p22phox, a subunit of the NADH/NADPH oxidase system. Design: we investigated whether the C242T nucleotide transition is associated with the presence of coronary artery disease (CAD) in a population of 494 Caucasian Italians undergoing coronary angiography to diagnose the cause of chest pain. Results: the frequency of the T mutant allele that we found in 276 patients with angiographically documented CAD was significantly higher compared to what we observed in 218 subjects with normal coronary arteries (Controls) (respectively: 0.400 and 0.332, p < 0.01). The prevalence of the T allele was even stronger when we compared: 1) early onset (age ≤55) vs late onset (age ≥65) single-vessel CAD patients (respectively: 0.75 and 0.48, p < 0.05), and 2) the subgroup of CAD patients with at least one ≥98% stenosis in a coronary vessel vs those with no ≥98% stenosis in a coronary vessel (respectively: 0.425 and 0.365, p < 0.05). Conclusions: these results support the increased risk of developing early CAD and of having rapid progression of coronary stenosis in subjects carrying the C242T nucleotide transition among the Italian population.

Allelic variations in the CYBA gene of NADPH oxidase and risk of kidney complications in patients with type 1 diabetes

“…Higher NADPH oxidase activity was observed for both alleles in different studies [46,47]. Associations with arterial hypertension [29,30] or coronary artery disease [48,49], among other phenotypes, were also reported for both alleles in different studies. Of particular interest are the reports, in cross-sectional studies and/or studies with a small sample size, of T-allele (72Tyr) association with nephropathy in type 1 diabetic patients [31], with established or advanced nephropathy in type 2 diabetic patients, but only in interaction with smoking [50], and with dialysis requirement or hospital mortality following acute renal failure [51].…”

Three common polymorphisms in theCYBAgene form a haplotype associated with decreased ROS generation

“…This topic has been recently reviewed [San Jose et al, 2008], and it is apparent that there are important discrepancies among the results of the different studies. Looking, for example, at the data on c.214T4C in cardiovascular diseases, there are at least six studies suggesting that it is protective [Cahilly et al, 2000;Cai et al, 1999;Hayaishi-Okano et al, 2003;Ishii et al, 2004;Ito et al, 2000;Nasti et al, 2006], four suggesting that it is a risk factor [Grahl et al, 2007;He et al, 2007;Inoue et al, 1998;Moreno et al, 2006], and three studies suggesting that it does not have an impact on the disease [Gardemann et al, 1999;Mata-Balaguer et al, 2004;Zafari et al, 2002]. Thus, this SNP by itself is unlikely to have a major impact on the development of cardiovascular diseases.…”

Molecular genetics of atherosclerosis

“…The relationship of the C242T polymorphism in the p22-phox gene with atherosclerosis has been investigated with conXicting results (Soccio et al 2005). The C242T mutation has been associated with either a protective eVect in atherosclerosis (Fan et al 2007a, b;Hayaishi-Okano et al 2003;Inoue et al 1998), an increased risk of early CAD (Cai et al 1999;Nasti et al 2006) or no eVect on atherosclerosis (Gardemann et al 1999;Saha et al 1999). A recent metaanalysis of data from studies evaluating association between the C242T polymorphism of the p22phox component of NADPH oxidase and CAD suggests that the T allele does not have a signiWcant eVect in the Caucasians but may have a protective role in the Asian population (Di Castelnuovo et al 2008).…”