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The C242T CYBA Polymorphism as a Major Determinant of NADPH Oxidase Activity in Patients with Cardiovascular Disease

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Single nucleotide polymorphisms (SNP) in the CYBA gene encoding p22phox have been associated with respiratory burst and cardiovascular phenotypes. We previously reported a reduced phagocytic respiratory burst activity in healthy adults with the C242T SNP, but found no correlation between CYBA SNPs and coronary artery disease (CAD) phenotype. Using lymphoblastoid cells, we hypothesized that CYBA SNPs affect enzyme activity in patients with cardiovascular disease (CVD), but would not be associated with angiographic severity of CAD due to confounding by risk factors. We established lymphoblastoid cell lines from patients with CVD and genotyped the study cohort for CYBA SNPs and phenotyped each subject's coronary angiogram for CAD severity. As quantified by electron spin resonance, superoxide production in picomoles per 106 resting lymphoblastoid cells per minute for the CC, CT, and TT genotypes of the C242T SNP were 16.2±1.4, n=70, 11.9±0.7, n=87, and 11.9±1.5, n=28, respectively (P=0.002). The -930A/G and A640G SNPs did not affect superoxide production (P>0.2). Expression of p22phox was not affected as determined by real-time RT-PCR and Western blot analysis. The C242T CYBA SNP is associated with altered NADPH oxidase activity in lymphoblastoid cells of patients with CVD. By reducing the influence of confounding environmental factors, lymphoblastoid cell lines could serve as a tool to assess direct genotype/phenotype interactions of candidate genes known to affect atherosclerosis.





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Keywords: CYBA; NADPH oxidase; SNP; atherosclerosis; coronary heart disease; functional genomics; genetic association; genotype-phenotype relationship

Document Type: Research Article

Publication date: July 1, 2009

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  • Cardiovascular & Hematological Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of new Cardiovascular & Hematological Agents. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics in Cardiovascular & Hematological medicinal chemistry.

    Cardiovascular & Hematological Agents in Medicinal Chemistry
    is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in cardiovascular & hematological drug discovery.
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