Cyclooxygenase-2 Genetic Polymorphism and Stroke Subtypes in Chinese

• Published in: Journal of molecular neuroscience Vol. 51; no. 2; pp. 467 - 473
• Main Authors: Chen, Guo-zhong, Shan, Xiao-yun, Cheng, Gan-ping, Tao, Hong-miao
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.10.2013; Springer Nature B.V
• Subjects: Adult; Aged; Arteries; Atherosclerosis; Biomedical and Life Sciences; Biomedicine; Brain Ischemia - genetics; Case-Control Studies; Cell Biology; China; Cyclooxygenase 2 - genetics; Enzymes; Etiology; Female; Genes; Genetic Predisposition to Disease; Haplotypes; Humans; Investigations; Ischemia; Linkage Disequilibrium; Male; Middle Aged; Neurochemistry; Neurology; Neurosciences; Pallets; Polymorphism; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Proteomics; Stroke; Stroke - genetics; Veins & arteries; China; Zhejiang China; Small vessel occlusion; Large artery atherosclerosis; Cyclooxygenase-2; Linkage disequilibrium; Polymorphism
• ISSN: 0895-8696; 1559-1166
• DOI: 10.1007/s12031-013-0078-5

Background Cyclooxygenase-2 (COX-2) catalyzes the formation of prostaglandins that contribute to the inflammation in atherosclerosis. The aim of the present study was to investigate the relationship between two polymorphisms (−1195G>A and -765G>C) in the COX-2 gene and subtypes of ischemic stroke in a Chinese population. Methods Genomic DNA of 224 patients with large artery atherosclerosis (LAA), 329 patients with small vessel occlusion (SVO), and 450 controls were genotyped for the COX-2 1195G>A (rs689466) and -765G>C (rs20417) polymorphisms using polymerase chain reaction–restriction fragment length polymorphism. Chi-square test and logistic regression analysis were performed for association analysis. Results The frequencies of variant allele with -1195G>A and -765G>C polymorphisms were 0.46 and 0.22, respectively. The -1195GA genotype and 1195A allele carriers were identified independently to be related with ischemic stroke (adjusted OR = 1.51, 95 % CI: 1.09–2.10, P =  0.02; OR = 1.45, 95 % CI: 1.06–1.97, P =  0.02) and SVO (adjusted OR = 1.57, 95 % CI: 1.07–2.30, P =  0.02; OR = 1.50, 95 % CI: 1.05–2.16, P =  0.03). In contrast, the 1195G>A polymorphism was not associated with LAA. No relationship between the -765G>C polymorphism and risk of either ischemic stroke was observed. The linkage disequilibrium analysis showed that -1195G>A and -765G>C SNPs are moderate linkage disequilibrium in this study population ( D ′ = 0.72, r 2  = 0.16). Compared with G-1195-G-765 haplotype, the haplotype of A-1195-G-765 showed significant increased risk of ischemic stroke (OR = 1.27, 95 % CI: 1.05–1.54, P =  0.02) and SVO (OR = 1.27, 95 % CI: 1.02–1.58, P =  0.03) but not LAA. Conclusions In conclusion, we found that -1195G>A polymorphism and A-1195-G-765 haplotype of COX-2 were associated with susceptibility to ischemic stroke in a Chinese population. The effects were confined to SVO among the stroke subtypes rather than to LAA.