Association Of COX-2 Gene Haplotype In The Chinese Han Population With Atherothrombotic Ischemic Stroke

BackgroundAtherothrombotic ischemic stroke represents a major leading cause of morbidity, mortality and disability in Human being.It is recognized to be complex disorders that likely result from multifaceted interactions between an individual's genetic makeup and environmental factors.The individual's genetic makeup is believed to play an essential role in the clinical outcomes of ischemic stroke by epidemiologic studies and experimental studies.Inflammation-induced COX-2 expression is significantly associated with ischemic stroke pathogenesis.To investigate whether the polymorphism of COX-2 gene is associated with atherothrombotic ischemic stroke,we conducted a case-control study.ObjectiveThe aim of this study was to evaluate regulation,whether COX-2 gene polymorphisms or its haplotypes might be associated with susceptibility to atherothrombotic ischemic stroke in the Chinese Hart population.MethodsThe study included 604 patients with atherothrombotic ischemic stroke and 626 sex,age-matched healthy controls.Two COX-2 gene polymorphisms(-1195G/A and 8473C/T) were determined using the high-throughput SNP genotyping by single-tube PCR with Tin-shift primers method.We used the software PHASE2.0 to construct the haplotype of every individual.The logistic regression model was used to analyze the statistical association of genotypes or haplotypes in two groups adjusted for age,gender,smoking,BMI,EH,DM and HL. ResultsA significant difference was observed between patients and controls.No significant difference was found in the COX-2-1195G/A between patients and controls(P＞0.05).The frequency of genotype 8473CT was significantly higher in patients than in controls(OR=1.329,95%CT=1.028-1.719).By haplotype analysis, the frequency of haplotype AC(-1195A and 8473C) revealed a significant difference in the patients in comparison to controls(P=0.013).Logistic regression analysis showed individuals owing the haplotype AC had an increased possibility of ischemic stroke(OR=1.372,95%CI=1.070-1.760,adjusted for confounding factors)Conclusion1.The two single nucleotide polymorphisms(SNP) of COX-2 gene were present in Chinese Han population(G/A,T/C).2.The SNP 8473T/C was associated with susceptibility to atherothrombotic ischemic stroke in Chinese Han population.3.The haplotype AC(-1195A and 8473C) may be a crucial risk factor of genetic susceptibility to atherothrombotic ischemic stroke in Chinese Han population.