The effect of p22-PHOX (CYBA) polymorphisms on premature coronary artery disease (≤ 40 years of age)

Abstract

Acute myocardial infarction at a young age is associated with high morbidity and long-term mortality. The NADPH oxidase system as a main source of reactive oxygen species in vascular cells has been implicated in development and progression of coronary artery disease (CAD). In our study, we investigated the effect of polymorphisms in the p22-PHOX (CYBA) gene on CAD in young patients (≤ 40 years). We prospectively recruited 302 subjects into our multi-centre case control study, including 102 young myocardial infarction patients (≤ 40 years) from two high-volume cardiac catheterisation hospitals and frequency-matched them on age, gender, and center to 200 hospital controls in an approximate 2:1 ratio per case patient. The homozygote c.-930A>G promoter polymorphism was significantly more prevalent in the controls than in the infarction patients. In the adjusted logistic regression analysis, we detected a protective effect of the c.-930A>G promoter polymorphism against premature myocardial infarction. Using a log-additive/per-allele model, we detected an unadjusted odds ratio (OR) of 0.63 (95% confidence interval [CI] 0.45-0.9, p-value 0.011). In the adjusted model the association was more pronounced with an OR of 0.5 (95% CI 0.3-0.81, p-value 0.005). The C242T polymorphism and the 640A>G polymorphism did not differ significantly between the study groups. Furthermore we could not detect a significant effect for these polymorphisms in the logistic regression analysis. The present study suggests a protective association between the c.-930A>G promoter polymorphism in the p22-PHOX (CYBA) gene and the development of myocardial infarction in young individuals (≤ 40 years).

Meta-analysis of C242T polymorphism in CYBA genes: risk of acute coronary syndrome is lower in Asians but not in Caucasians

“…It has been reported that physical activity could modify this genetic effect of the CYBA gene (Zhu et al, 2012). 640A>G polymorphism in the CYBA gene have also been implicated in the development of cardiovascular disease (Goliasch et al, 2011;Xu et al, 2014). Further researches will be needed to clarify the possible correlation of the three haplotypes of the CYBA gene.…”

“…Three publications did not meet the requirements of HWE (P HWE <0.05) (Mata-Balaguer et al, 2004;Morgan et al, 2007;Hashad et al, 2014). Finally, a total of 10 casecontrol studies were retrieved on ACS and the CYBA C242T polymorphism (Gardemann et al, 1999;Stanger et al, 2001;Yamada et al, 2002;Murase et al, 2004;Vasiliadou et al, 2006;Macías-Reyes et al, 2008;Katakami et al, 2010;de Caterina et al, 2011;Goliasch et al, 2011;Narne et al, 2012).…”

“…All the included studies were conducted from 1999 to 2012, with 6102 ACS patients and 8669 controls. MI was employed as the primary endpoint in five studies (Yamada et al, 2002;Vasiliadou et al, 2006;Katakami et al, 2010;de Caterina et al, 2011;Goliasch et al, 2011), while MI and unstable angina were taken as the endpoint in two studies (Murase et al, 2004;Macías-Reyes et al, 2008). The endpoint of three studies was CAD, and MI was taken as the endpoint in subgroup analysis (Gardemann et al, 1999;Stanger et al, 2001;Narne et al, 2012).…”

Gene Polymorphism and Coronary Heart Disease

“…The NADPH oxidase system as a main source of reactive oxygen species in vascular cells has been implicated in development and progression of CAD. In contrast, some gene variants, such as c.-930A>G in the promoter region of p22-PHOX gene have been shown to have protective effects 107 .…”

Oxidative stress at high altitude: genotype&ndash;phenotype correlations

“…This protein forms a critical component of the nicotinamide adenine dinucleotide phosphate oxidase system, which is involved in the production of superoxide anion, a reactive free radical. 118 These superoxides are involved in causing oxidative stress, one of the debilitating effects of HA exposure, leading to HAPE. 29 The gene has functional variants that have been associated with various oxidative stress-related diseases.…”