Interaction between COX-1 and COX-2 increases susceptibility to ischemic stroke in a Chinese population
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 to explain the association between these polymorphisms and ischemic stroke risk determine whether gene–gene interaction between these genes increase 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 and 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 or its 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 or its subtypes.