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BMC Neurology
Published in: BMC Neurology 1/2019

Open Access 01-12-2019 | Stroke | Research article

Interaction between COX-1 and COX-2 increases susceptibility to ischemic stroke in a Chinese population

Authors: Lei Zhao, Jinghuan Fang, Muke Zhou, Jie Zhou, Lihua Yu, Ning Chen, Li He

Published in: BMC Neurology | Issue 1/2019

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Abstract

Background

Mutations of cyclooxygenase gene (COX gene) may increase the susceptibility of ischemic stroke. We investigated five variants (rs5788, rs1330344, rs3842788, rs20417, and rs689466) of two COX genes in order to explaining the association between these polymorphisms and we also investigated the association between these variants and ischemic stroke risk to determine whether gene–gene interaction between these genes increases the susceptibility of ischemic stroke or its subtypes.

Methods

A total of 1981 study subjects (1078 cases and 903 control subjects) were recruited. The interaction of multiple factors was investigated using Multifactor Dimensionality Reduction. The additive effect of single nucleotide polymorphisms on ischemic stroke or its subtypes were analyzed by multiple factor logistic regression.

Results

At COX-1(rs1330344), AA genotype carriers had a lower susceptibility of ischemic stroke (OR = 0.657, 95%CI = 0.437–0.988, P = 0.044), and A allele carriers had a lower susceptibility of ischemic stroke (OR = 0.812, 95%CI = 0.657–0.978, P = 0.029). At COX-1(rs3842788), AA genotype carriers had a higher susceptibility of ischemic stroke (OR = 5.203, 95% CI = 1.519–5.159, P = 0.016). At COX-2 (rs689466), AA genotype carriers had a higher susceptibility of large-artery atherosclerosis (OR = 1.404, 95% CI = 1.019–1.934, P = 0.038). COX-1(rs1330344, rs3842788) and COX-2 rs689466 interacted in SVO, but had no additive effect with ischemic stroke and other subtypes.

Conclusions

At rs1330344, AA genotype may reduce the susceptibility of ischemic stroke. At rs3842788, AA genotype may increase the susceptibility of ischemic stroke. At rs689466, AA genotype may increase the susceptibility of large-artery atherosclerosis (LAA). COX − 1(rs1330344, rs3842788) and COX-2 rs689466 interacted in small vessel occlusion (SVO), but had no additive effect with ischemic stroke and other subtypes.
Literature
1.
Roger VL. Heart disease and stroke statistics--2011 update: a report from the American Heart Association. Circulation. 2011;123(4):e18–e209.PubMedCrossRef
2.
Yang G, et al. Rapid health transition in China, 1990–2010: findings from the global burden of disease study 2010. Lancet. 2013;9882(9882):1987–2015.CrossRef
3.
4.
Rothwell PM, et al. Change in stroke incidence, mortality, case-fatality, severity, and risk factors in Oxfordshire, UK from 1981 to 2004 (Oxford vascular study). Lancet. 2004;363(9425):1925–33.PubMedCrossRef
5.
Rubattu S, Giliberti R, Volpe M. Etiology and pathophysiology of stroke as a complex trait ☆. Am J Hypertens. 2000;13(10):1139–48.PubMedCrossRef
6.
Rosengren A, et al. Association of psychosocial risk factors with risk of acute myocardial infarction in 11119 cases and 13648 controls from 52 countries (the INTERHEART study) : case-control study. Lancet. 2004;364(9438):953–62.PubMedCrossRef
7.
Emsley HCA, et al. An early and sustained peripheral inflammatory response in acute ischaemic stroke: relationships with infection and atherosclerosis. J Neuroimmunol. 2003;139(1–2):93–101.PubMedCrossRef
8.
Funk CD. Prostaglandins and leukotrienes: advances in eicosanoid biology. Science. 2001;294(5548):1871–5.PubMedCrossRef
9.
Calder PC. Polyunsaturated fatty acids and inflammatory processes: new twists in an old tale. Biochimie. 2009;91(6):791–5.PubMedCrossRef
10.
Solveig G, et al. The gene encoding phosphodiesterase 4D confers risk of ischemic stroke. Nat Genet. 2003;35(2):131–8.CrossRef
11.
Jesper M, Marcel K. Functional SNP in an Sp1-binding site of AGTRL1 gene is associated with susceptibility to brain infarction. Hum Mol Genet. 2007;16(6):630–9.CrossRef
12.
13.
Xu CQ, et al. Minor allele C of chromosome 1p32 single nucleotide polymorphism rs11206510 confers risk of ischemic stroke in the Chinese Han population. Stroke. 2010;41(8):1587–92.PubMedCrossRef
14.
Tomonaga M, et al. Functional SNP of ARHGEF10 confers risk of atherothrombotic stroke. Hum Mol Genet. 2010;19(6):1137–46.CrossRef
15.
Helgadottir, A., ., et al., Association between the gene encoding 5-lipoxygenase-activating protein and stroke replicated in a Scottish population. Am J Hum Genet, 2005. 76(3): p. 505–509.PubMedPubMedCentralCrossRef
16.
Warner TD, Mitchell JA. Cyclooxygenases: new forms, new inhibitors, and lessons from the clinic. FASEB J. 2004;18(7):790–804.PubMedCrossRef
17.
Cipollone, F., ., et al., Overexpression of functionally coupled cyclooxygenase-2 and prostaglandin E synthase in symptomatic atherosclerotic plaques as a basis of prostaglandin E(2)-dependent plaque instability. Circulation, 2001. 104(8): p. 921–927.PubMedCrossRef
18.
Vane J, Bakhle Y, Botting RM. Cyclooxygenases 1 and 2. Annu Rev Pharmacol Toxicol. 1998;38(1):97–120.PubMedCrossRef
19.
Maree AO, et al. Cyclooxygenase-1 haplotype modulates platelet response to aspirin. J Thromb Haemost. 2005;3(10):2340–5.PubMedCrossRef
20.
Kohsaka S, 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):926–30.PubMedCrossRef
21.
Donatella C, et al. The COX-2 G/C −765 polymorphism may modulate the occurrence of cerebrovascular ischemia. Blood Coagul Fibrinolysis. 2006;17(2):93–6.CrossRef
22.
Francesco C, et al. A polymorphism in the cyclooxygenase 2 gene as an inherited protective factor against myocardial infarction and stroke. JAMA. 2004;291(18):2221–8.CrossRef
23.
Cao L, et al. Impacts of COX-1 gene polymorphisms on vascular outcomes in patients with ischemic stroke and treated with aspirin. Gene. 2014;546(2):172–6.PubMedCrossRef
24.
Kim DH, et al. A promoter polymorphism (rs17222919, −1316T/G) of ALOX5AP is associated with intracerebral hemorrhage in Korean population. Prostaglandins Leukot Essent Fat Acids. 2011;85(3–4):115–20.CrossRef
25.
Li W, et al. Cyclooxygenase-2 (COX-2) G-765C is a protective factor for coronary artery disease but not for ischemic stroke: a meta-analysis. Atherosclerosis. 2009;207(2):492–5.PubMedCrossRef
26.
Chen GZ, et al. Cyclooxygenase-2 genetic polymorphism and stroke subtypes in Chinese. J Mol Neurosci. 2013;51(2):467–73.PubMedCrossRef
27.
Stroke--1989. Recommendations on stroke prevention, diagnosis, and therapy. Report of the WHO Task Force on Stroke and other Cerebrovascular Disorders. Stroke. 1989;20(10):1407–31.
28.
Adams HP, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of org 10172 in acute stroke treatment. Stroke. 1993;24(1):35–41.PubMedCrossRef
29.
Hallstrom AP, Cobb LA, Ray R. Smoking as a risk factor for recurrence of sudden cardiac arrest. N Engl J Med. 1986;314(5):271–5.PubMedCrossRef
30.
Langaee T, Ronaghi M. Genetic variation analyses by pyrosequencing. Mutat Res. 2005;573(1–2):96–102.PubMedCrossRef
31.
Tetsuya K, et al. Characterization of the human gene (PTGS2) encoding prostaglandin-endoperoxide synthase 2. Eur J Biochem. 1994;221(3):889–97.CrossRef
32.
Avinoam S, Alex S. Tricuspid regurgitation in mitral valve disease incidence, prognostic implications, mechanism, and management. J Am Coll Cardiol. 2009;53(5):401–8.CrossRef
33.
Vucević D, et al. Inflammatory process in atherogenesis: new facts about old flame. Med Pregl. 2012;65(9–10):388–95.PubMedCrossRef
34.
Yi XY, et al. Interaction between ALOX5AP-SG13S114A/T and COX-2-765G/C increases susceptibility to cerebral infarction in a Chinese population. Genet Mol Res. 2013;12(2):1660–9.PubMedCrossRef
35.
Lemaitre RN, et al. Variation in eicosanoid genes, non-fatal myocardial infarction and ischemic stroke. Atherosclerosis. 2009;204(2):e58–63.PubMedCrossRef
36.
AD P, et al. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA. 2001;286(3):327–34.CrossRef
37.
YL K, JK W. Association of a promoter variant in the inducible cyclooxygenase-2 gene (PTGS2) with type 2 diabetes mellitus in Pima Indians. Hum Genet. 2003;113(5):377–81.CrossRef
38.
Ozbayer C, et al. Genetic variant in the 3′-untranslated region of the COX2 gene is associated with type 2 diabetes: a hospital-based case-control study. Prostaglandins Leukot Essent Fat Acids. 2018;137:39–42.CrossRef
39.
Merhi M, et al. Impact of inflammation, gene variants, and cigarette smoking on coronary artery disease risk. Inflamm Res. 2015;64(6):415–22.PubMedCrossRef
Metadata
Title
Interaction between COX-1 and COX-2 increases susceptibility to ischemic stroke in a Chinese population
Authors
Lei Zhao
Jinghuan Fang
Muke Zhou
Jie Zhou
Lihua Yu
Ning Chen
Li He
Publication date
01-12-2019
Publisher
BioMed Central
Keyword
Stroke
Published in
BMC Neurology / Issue 1/2019
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-019-1505-1

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