Association between the nicotinamide adenine dinucleotide phosphate oxidase p22phox gene ‑A930G polymorphism and intracerebral hemorrhage

Zhou,Yuan; Zhao,Ying‑Chun

doi:10.3892/mmr.2015.3154

Association between the nicotinamide adenine dinucleotide phosphate oxidase p22phox gene ‑A930G polymorphism and intracerebral hemorrhage

Authors:
- Yuan Zhou
- Ying‑Chun Zhao
View Affiliations

Affiliations: Department of Neurology, Jiuting Hospital, Shanghai 201600, P.R. China, Department of Neurology, Songjiang Central Hospital, Shanghai 201600, P.R. China
Published online on: January 7, 2015 https://doi.org/10.3892/mmr.2015.3154
Pages: 3511-3516

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The present study aimed to evaluate whether the ‑A930G polymorphism of the nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase p22phox gene is involved in intracerebral hemorrhage (ICH) in the Chinese Han population. In the present case‑control investigation, the subjects included 118 patients with ICH and 147 healthy controls. The ‑A930G polymorphism was determined using polymerase chain reaction and restriction fragment length polymorphism. Furthermore, the correlation between the ‑A930G gene polymorphism and ICH was evaluated using statistical analyses. The distribution of p22phox ‑A930G genotypes differed significantly between the two groups (P=0.003), with the AA, AG and GG genotype frequencies being 61.9, 29.3 and 8.8% in the control group and 40.7, 45.8 and 13.6% in the ICH group, respectively. The G allele frequency was significantly higher in patients with ICH compared with healthy controls (36.4 vs. 23.5%; P<0.05), however, the opposite was observed in the frequency of the A allele (63.6 vs. 76.5%; P<0.05). Binary logistic regression analysis revealed that genetic mutations of the p22phox ‑A930G gene were independent risk factors of ICH (odds ratio, 2.196; 95% confidence interval, 1.003‑4.586; P=0.009). In addition, certain conventional factors were associated with increased risk of ICH, including elevated blood pressure, increased levels of glucose and triglycerides in the blood, a history of hypertension and smoking. The ‑A930G polymorphism of the p22phox gene may affect the susceptibility to ICH and certain haplotypes of the gene may be associated with a higher susceptibility to ICH.

View Figures

View References

1	Hua Y, Keep RF, Gu Y and Xi G: Thrombin and brain recovery after intracerebral hemorrhage. Stroke. 40:S88–S89. 2009. View Article : Google Scholar :
2	Dong XQ, Du Q, Yu WH, et al: Plasma resistin, associated with single nucleotide polymorphism -420, is correlated with C-reactive protein in Chinese Han patients with spontaneous basal ganglia hemorrhage. Genet Mol Res. 11:1841–1850. 2012. View Article : Google Scholar : PubMed/NCBI
3	Khatri R, Tariq N, Vazquez G, et al: Outcomes after nontraumatic subarachnoid hemorrhage at hospitals offering angioplasty for cerebral vasospasm: a national level analysis in the United States. Neurocrit Care. 15:34–41. 2011. View Article : Google Scholar
4	Aronowski J and Zhao X: Molecular pathophysiology of cerebral hemorrhage: secondary brain injury. Stroke. 42:1781–1786. 2011. View Article : Google Scholar : PubMed/NCBI
5	Qureshi AI, Mendelow AD and Hanley DF: Intracerebral haemorrhage. Lancet. 373:1632–1644. 2009. View Article : Google Scholar : PubMed/NCBI
6	Kim H, Crago E, Kim M, et al: Cerebral vasospasm after sub-arachnoid hemorrhage as a clinical predictor and phenotype for genetic association study. Int J Stroke. 8:620–625. 2013. View Article : Google Scholar
7	Taniyama Y and Griendling KK: Reactive oxygen species in the vasculature: molecular and cellular mechanisms. Hypertension. 42:1075–1081. 2003. View Article : Google Scholar : PubMed/NCBI
8	Li J, Zhou K, Meng X, et al: Increased ROS generation and SOD activity in heteroplasmic tissues of transmitochondrial mice with A3243G mitochondrial DNA mutation. Genet Mol Res. 7:1054–1062. 2008. View Article : Google Scholar : PubMed/NCBI
9	Cheng JC, Cheng HP, Tsai IC and Jiang MJ: ROS-mediated downregulation of MYPT1 in smooth muscle cells: a potential mechanism for the aberrant contractility in atherosclerosis. Lab Invest. 93:422–433. 2013. View Article : Google Scholar : PubMed/NCBI
10	Ng CK, Deshpande SS, Irani K and Alevriadou BR: Adhesion of flowing monocytes to hypoxia-reoxygenation-exposed endothelial cells: role of Rac1, ROS, and VCAM-1. Am J Physiol Cell Physiol. 283:C93–C102. 2002. View Article : Google Scholar : PubMed/NCBI
11	Wang Y and Tabas I: Emerging roles of mitochondria ROS in atherosclerotic lesions: causation or association? J Atheroscler Thromb. 21:381–390. 2014. View Article : Google Scholar : PubMed/NCBI
12	Patel RP, Moellering D, Murphy-Ullrich J, Jo H, Beckman JS and Darley-Usmar VM: Cell signaling by reactive nitrogen and oxygen species in atherosclerosis. Free Radic Biol Med. 28:1780–1794. 2000. View Article : Google Scholar : PubMed/NCBI
13	Qin YW, Peng J, Liang BY, et al: The A930G polymorphism of P22phox (CYBA) gene but not C242T variation is associated with hypertension: a meta-analysis. PLoS One. 8:e824652013. View Article : Google Scholar :
14	Muller G and Morawietz H: Nitric oxide, NAD(P)H oxidase, and atherosclerosis. Antioxid Redox Signal. 11:1711–1731. 2009. View Article : Google Scholar : PubMed/NCBI
15	Akasaki T, Ohya Y, Kuroda J, et al: Increased expression of gp91phox homologues of NAD(P)H oxidase in the aortic media during chronic hypertension: involvement of the renin-angiotensin system. Hypertens Res. 29:813–820. 2006. View Article : Google Scholar
16	Ushio-Fukai M, Zafari AM, Fukui T, Ishizaka N and Griendling KK: 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 Biol Chem. 271:23317–23321. 1996. View Article : Google Scholar : PubMed/NCBI
17	Fraser PA: The role of free radical generation in increasing cerebrovascular permeability. Free Radic Biol Med. 51:967–977. 2011. View Article : Google Scholar : PubMed/NCBI
18	Papaharalambus CA and Griendling KK: Basic mechanisms of oxidative stress and reactive oxygen species in cardiovascular injury. Trends Cardiovasc Med. 17:48–54. 2007. View Article : Google Scholar : PubMed/NCBI
19	Seligmann C, Schimmer M, Leitsch T, et al: A thrombocyte-induced myocardial dysfunction in the ischemic and reperfused guinea pig heart is mediated by reactive oxygen species. Free Radic Biol Med. 29:1244–1251. 2000. View Article : Google Scholar : PubMed/NCBI
20	Collins-Underwood JR, Zhao W, Sharpe JG and Robbins ME: NADPH oxidase mediates radiation-induced oxidative stress in rat brain microvascular endothelial cells. Free Radic Biol Med. 45:929–938. 2008. View Article : Google Scholar : PubMed/NCBI
21	Ding H, Aljofan M and Triggle CR: Oxidative stress and increased eNOS and NADPH oxidase expression in mouse microvessel endothelial cells. J Cell Physiol. 212:682–689. 2007. View Article : Google Scholar : PubMed/NCBI
22	San José G, Moreno MU, Oliván S, et al: Functional effect of the p22phox -930A/G polymorphism on p22phox expression and NADPH oxidase activity in hypertension. Hypertension. 44:163–169. 2004. View Article : Google Scholar : PubMed/NCBI
23	Goliasch G, Wiesbauer F, Grafl A, et al: The effect of p22-PHOX (CYBA) polymorphisms on premature coronary artery disease (≤ 40 years of age). Thromb Haemost. 105:529–534. 2011. View Article : Google Scholar
24	Zalba G, San José G, Moreno MU, Fortuño A and Díez J: Nadph oxidase-mediated oxidative stress: genetic studies of the p22(phox) gene in hypertension. Antioxid Redox Signal. 7:1327–1336. 2005. View Article : Google Scholar : PubMed/NCBI
25	Xaplanteris P, Vlachopoulos C, Baou K, et al: The effect of p22(phox) -930A/G, A640G and C242T polymorphisms of NADPH oxidase on peripheral and central pressures in healthy, normotensive individuals. Hypertens Res. 33:814–818. 2010. View Article : Google Scholar : PubMed/NCBI
26	Moreno MU, San José G, Fortuño A, Beloqui O, Díez J and Zalba G: The C242T CYBA polymorphism of NADPH oxidase is associated with essential hypertension. J Hypertens. 24:1299–1306. 2006. View Article : Google Scholar : PubMed/NCBI
27	Fan M, Raitakari OT, Kähönen M, et al: The association between cigarette smoking and carotid intima-media thickness is influenced by the -930A/G CYBA gene polymorphism: the Cardiovascular Risk in Young Finns Study. Am J Hypertens. 22:281–287. 2009. View Article : Google Scholar : PubMed/NCBI