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

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

doi:10.1186/s12883-019-1505-1

Lei Zhao, Li He + Show 5 more

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https://doi.org/10.1186/s12883-019-1505-1

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Abstract

BackgroundMutations 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.MethodsA 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.ResultsAt 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.ConclusionsAt 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.

Highlights

Mutations of cyclooxygenase gene (COX gene) may increase the susceptibility of ischemic stroke
At cyclooxygenase or prostaglandin oxidase (COX)-1(rs1330344), compared to the GG genotype, the arachidonic acid (AA) genotype carriers had a lower susceptibility of ischemic stroke, and this difference remained significant in multivariate analysis by adjusting for age, gender and traditional risk factors (OR = 0.657, 95% CI = 0.437– 0.988, P = 0.044)
At rs1330344, AA genotype may reduce the susceptibility of ischemic stroke, and Cardioembolic stroke (CES) or small vessel occlusion (SVO)

Summary

Introduction

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 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. Ischemic stroke was characterized by several etiological factors and likely affected by various genes, environments, lifestyles, and other causes; which could produce complex high-order interactions to this disease [3,4,5,6]. The mutation of some gene involved in the inflammatory response can cause the internal environment disturbance which might lead to the occurrence and development process of atherosclerosis. Atherosclerosis is a kind of multifactorial disease, involving many factors such as gene, environment, metabolic interaction at the

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