Correlation between -765G/C Polymorphism of Cyclooxygenase-2 Gene and the Risk of Ischemic Stroke: A Meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

 CHENZhong-yun , WEIJing-pei , ZHANGJie , SHIZhe ,  XINGYan

Department of Neurology, Aviation General Hospital, Beijing 100012, China;

Corresponding author：

XINGYan, Email: drxingyan@163.com

Keywords：

Ischemia stroke; Cyclooxygenase-2; Polymorphism; Meta-analysis; Case-control study

DOI：

10.7507/1672-2531.20160011

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Objective To explore the correlation between -765G/C polymorphism of cyclooxygenase-2 (COX-2) gene and the risk of ischemic stroke (IS). Methods PubMed, CBM, The Cochrane Library (Issue 3, 2015), CNKI, CBM, VIP and WanFang Data were searched from inception to March 2015 to collect case-control or nested case-control studies about -765G/C polymorphism of COX-2 gene and the risk of IS. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.1 software and Stata 12.0 software. Results A total of 10 studies involving 2611 cases and 18589 controls were included. The results of meta-analysis showed that, there was no correlation between -765G/C polymorphism and the risk of IS (GC+CC vs. GG: OR=1.05, 95%CI 0.88 to 1.25, P=0.620; CC vs. GG+GC: OR=1.04, 95%CI 0.83 to 1.30, P=0.730; GC vs. GG: OR=1.04, 95%CI 0.87 to 1.25, P=0.630; CC vs. GG: OR=1.09, 95%CI 0.86 to 1.36, P=0.480; C vs. G: OR=1.03, 95%CI 0.89 to 1.20, P=0.700). Subgroup analysis results showed that, the COX-2 gene -765G/C polymorphism was a risk factor for IS in African-Americans (GC+CC vs. GG: OR=1.42, 95%CI 1.12 to 1.78, P=0.003; GC vs. GG: OR=1.39, 95%CI 1.09 to 1.78, P=0.008; CC vs. GG: OR=1.51, 95%CI 1.04 to 2.18, P=0.030; C vs. G: OR=1.27, 95%CI 1.08 to 1.51, P=0.004), but not in Asians and Caucasians. Conclusion Current evidence shows that -765G/C polymorphism of COX-2 gene may be a genetic risk factor for IS in African-Americans, but not in Asians and Caucasians. Due to the limited quantity and quality of the included studies, more high quality studies are needed to verify the above conclusion.

Citation： CHENZhong-yun, WEIJing-pei, ZHANGJie, SHIZhe, XINGYan. Correlation between -765G/C Polymorphism of Cyclooxygenase-2 Gene and the Risk of Ischemic Stroke: A Meta-analysis. Chinese Journal of Evidence-Based Medicine, 2016, 16(1): 48-53. doi: 10.7507/1672-2531.20160011 Copy

1.	Yang G, Wang Y, Zeng Y, et al. Rapid health transition in China, 1990-2010: findings from the Global Burden of Disease Study 2010. Lancet, 2013, 381(9882): 1987-2015.
2.	Matarin M, Singleton A, Hardy J, et al. The genetics of ischaemic stroke. J Intern Med, 2010, 267(2): 139-155.
3.	Rubattu S, Giliberti R, Volpe M. Etiology and pathophysiology of stroke as a complex trait. Am J Hypertens, 2000, 13(10): 1139-1148.
4.	Rodríguez-Yáñez M, Castillo J. Role of inflammatory markers in brain ischemia. Curr OpinNeurol, 2008, 21(3): 353-357.
5.	McGeer PL, McGeer EG, Yasojima K. Expression of COX-1 and COX-2 mRNAs in atheroscleroticplaques. Exp Gerontol, 2002, 37(7): 925-929.
6.	Colaizzo D, Fofi L, Tiscia G, et al. The COX-2 G/C -765 polymorphism may modulate the occurrence of cerebrovascular ischemia. Blood Coagul Fibrinolysis, 2006, 17(2): 93-96.
7.	Kohsaka S, Volcik KA, Folsom AR, et al. Increased risk of incident stroke associated with the cyclooxygenase 2 (COX-2) G-765C polymorphism in African-Americans: the Atherosclerosis Risk in Communities Study. Atherosclerosis, 2008, 196(2): 926-930.
8.	Lee CR, North KE, Bray MS, et al. Cyclooxygenase polymorphisms and risk of cardiovascular events: the Atherosclerosis Risk in Communities (ARIC) study. Clin Pharmacol Ther, 2008, 83(1): 52-60.
9.	Lemaitre RN, Rice K, Marciante K, et al. Variation in eicosanoid genes, non-fatal myocardial infarction and ischemic stroke. Atherosclerosis, 2009, 204(2): e58-63.
10.	Chen GZ, Shan XY, Cheng GP, et al. Cyclooxygenase-2 genetic polymorphism and stroke subtypes in Chinese. J Mol Neurosci, 2013, 51(2): 467-473.
11.	李健业, 吴海容, 李海先, 等. ALOX5APO基因、COX2基因和MMP9基因多态性与缺血性脑卒中相关性的研究. 齐鲁医学杂志, 2013, 28(4): 321-324.
12.	陈忠云, 李珊珊, 李婧, 等. 环氧化酶2基因多态性与中国汉族人群缺血性脑卒中及其亚型的关系研究. 中国全科医学, 2014, 17(17): 1959-1963.
13.	王凤, 郑维红, 马飞煜, 等. COX-2基因多态性与脑梗死的关系. 中国老年学杂志, 2010, 30(12): 3481-3482.
14.	Cipollone F, Rocca B, Patrono C. Cyclooxygenase-2 expression and inhibition in atherothrombosis. Arterioscler Thromb Vasc Biol, 2004, 24(2): 246-255.
15.	Li W, Xu J, Wang X, et al. Cyclooxygenase-2 (COX-2) G-765C is a protective factor for coronary artery disease but not for ischemic stroke: ameta-analysis. Atherosclerosis, 2009, 207(2): 492-495.
16.	Cipollone F, Toniato E, Martinotti S, et al. A polymorphism in the cyclooxygenase 2 gene as an inherited protective factor against myocardial infarction and stroke. JAMA, 2004, 291(18): 2221-2228.
17.	Lee C, Kong M. An interactive association of common sequence variants in the neuropeptide Y gene with susceptibility to ischemic stroke. Stroke, 2007, 38(10): 2663-2669.
18.	Kim Y, Lee C. The gene encoding transforming growth factor beta 1 confers risk of ischemic stroke and vascular dementia. Stroke, 2006, 37(11): 2843-2845.

1. Yang G, Wang Y, Zeng Y, et al. Rapid health transition in China, 1990-2010: findings from the Global Burden of Disease Study 2010. Lancet, 2013, 381(9882): 1987-2015.
2. Matarin M, Singleton A, Hardy J, et al. The genetics of ischaemic stroke. J Intern Med, 2010, 267(2): 139-155.
3. Rubattu S, Giliberti R, Volpe M. Etiology and pathophysiology of stroke as a complex trait. Am J Hypertens, 2000, 13(10): 1139-1148.
4. Rodríguez-Yáñez M, Castillo J. Role of inflammatory markers in brain ischemia. Curr OpinNeurol, 2008, 21(3): 353-357.
5. McGeer PL, McGeer EG, Yasojima K. Expression of COX-1 and COX-2 mRNAs in atheroscleroticplaques. Exp Gerontol, 2002, 37(7): 925-929.
6. Colaizzo D, Fofi L, Tiscia G, et al. The COX-2 G/C -765 polymorphism may modulate the occurrence of cerebrovascular ischemia. Blood Coagul Fibrinolysis, 2006, 17(2): 93-96.
7. Kohsaka S, Volcik KA, Folsom AR, et al. Increased risk of incident stroke associated with the cyclooxygenase 2 (COX-2) G-765C polymorphism in African-Americans: the Atherosclerosis Risk in Communities Study. Atherosclerosis, 2008, 196(2): 926-930.
8. Lee CR, North KE, Bray MS, et al. Cyclooxygenase polymorphisms and risk of cardiovascular events: the Atherosclerosis Risk in Communities (ARIC) study. Clin Pharmacol Ther, 2008, 83(1): 52-60.
9. Lemaitre RN, Rice K, Marciante K, et al. Variation in eicosanoid genes, non-fatal myocardial infarction and ischemic stroke. Atherosclerosis, 2009, 204(2): e58-63.
10. Chen GZ, Shan XY, Cheng GP, et al. Cyclooxygenase-2 genetic polymorphism and stroke subtypes in Chinese. J Mol Neurosci, 2013, 51(2): 467-473.
11. 李健业, 吴海容, 李海先, 等. ALOX5APO基因、COX2基因和MMP9基因多态性与缺血性脑卒中相关性的研究. 齐鲁医学杂志, 2013, 28(4): 321-324.
12. 陈忠云, 李珊珊, 李婧, 等. 环氧化酶2基因多态性与中国汉族人群缺血性脑卒中及其亚型的关系研究. 中国全科医学, 2014, 17(17): 1959-1963.
13. 王凤, 郑维红, 马飞煜, 等. COX-2基因多态性与脑梗死的关系. 中国老年学杂志, 2010, 30(12): 3481-3482.
14. Cipollone F, Rocca B, Patrono C. Cyclooxygenase-2 expression and inhibition in atherothrombosis. Arterioscler Thromb Vasc Biol, 2004, 24(2): 246-255.
15. Li W, Xu J, Wang X, et al. Cyclooxygenase-2 (COX-2) G-765C is a protective factor for coronary artery disease but not for ischemic stroke: ameta-analysis. Atherosclerosis, 2009, 207(2): 492-495.
16. Cipollone F, Toniato E, Martinotti S, et al. A polymorphism in the cyclooxygenase 2 gene as an inherited protective factor against myocardial infarction and stroke. JAMA, 2004, 291(18): 2221-2228.
17. Lee C, Kong M. An interactive association of common sequence variants in the neuropeptide Y gene with susceptibility to ischemic stroke. Stroke, 2007, 38(10): 2663-2669.
18. Kim Y, Lee C. The gene encoding transforming growth factor beta 1 confers risk of ischemic stroke and vascular dementia. Stroke, 2006, 37(11): 2843-2845.

Chinese Journal of Evidence-Based Medicine

Correlation between -765G/C Polymorphism of Cyclooxygenase-2 Gene and the Risk of Ischemic Stroke: A Meta-analysis

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