P22phox
p22phox Protein, also known as the human neutrophil
Protein structure and gene function
Cytochrome b is a heterodimer of two
Genetic polymorphisms and link to coronary artery disease
Oxidative stress in the vasculature induced by ROS (particularly the
The C242T polymorphism occurs in exon 4 and results in a histidine to tyrosine amino acid substitution[1] in the p22phox protein. This leads to reduced NAD(P)H oxidase activity in human blood vessels and therefore a decreased production of ROS and vascular oxidative stress.[6] A 2014 meta-analysis indicated a protective role of this polymorphism for CAD in an Asian population due to reduced NAD(P)H oxidase activity.[2]
The A640G polymorphism is located in the 3’ untranslated region (UTR) of the CYBA gene and does not cause an amino acid substitution, however it has still been shown to have an effect on ROS generation.[7] Although this variation has been less extensively studied, it has also been linked to a decreased risk of CAD,[2] possibly due to decreased translational activity of the CYBA gene.[7] Specific mechanisms of this particular polymorphism are currently under investigation.[2]
References
- ^ a b c d Dinauer MC, Pierce EA, Bruns GA, Curnutte JT, Orkin SH. "Human neutrophil cytochrome b light chain (p22-phox). Gene structure, chromosomal location, and mutations in cytochrome-negative autosomal recessive chronic granulomatous disease." J Clin Invest. November 1990; 86(5): 1729-37.
- ^ a b c d e f Xu Q, Yuan F, Wu J. "Polymorphisms of C242T and A640G in CYBA Gene and the risk of coronary artery disease: A meta-analysis." PLoS One. 2014; 9(1): e84251
- ^ Ushio-Fukai M, Zafari A, Fukui T, Ishizaka N, Griendling K. "p22phox is a critical component of the superoxide-generating NADH/NADPH oxidase system and regulates angiotensin II induced hypertrophy in vascular smooth muscle cells." J Bio Chem. September 20, 1996; 271: 23317-21.
- ^ a b Azumi H et al. "Expression of NADH/NADPH oxidase p22phox in human coronary arteries." Circulation. October 5, 1999; 100(14): 1494-8.
- ^ Fortuna A, San Jose G, Moreno MU, Diez J, Zalba G. "Oxidative stress and vascular remodeling." Exp. Physiol. July 2005; 90(4): 457-62.
- ^ Tomasz J, et al. "Functional effect of the C242T polymorphism in the NAD(P)H oxidase p22phox gene on vascular superoxide production in atherosclerosis." Circulation. 2000; 102: 1744 – 1747.
- ^ a b Bedard K, Attar H, Bonnefont J, Jaquet V, Borel C, Plastre O, Stasia MJ, Antonarakis S, Krause KH. "Three common polymorphisms in the CYBA gene form a haplotype associated with decreased ROS generation." Hum. Mutat. July 2009; 30(7): 1123-1133