Cyclooxygenase-2 genetic polymorphism and stroke subtypes in Chinese.

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.