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.

Cyclooxygenase 2 genetic polymorphism may increase the risk of developing leukoaraiosis in Chinese.

Cyclooxygenase-2 (COX-2) is a key enzyme involved in the conversion of arachidonic acid into prostaglandins, which are important mediators of inflammation. To clarify the role of inflammation in the pathogenesis of cerebral small vessel disease (SVD), we investigate the possible modulating effect of the functional COX-2 polymorphisms -1195G > A (rs689466) and -765G > C (rs20417) on the risk for development of cerebral SVD in a Chinese population. Genomic DNA of 116 patients with lacunar infarction (LI), 334 patients with leukoaraiosis (LA) and 450 control subjects was genotyped for the COX-2 -1195G > A and -765G > C polymorphisms using polymerase chain reaction-restriction fragment length polymorphism. Distribution of genotypes and haplotypes in patients and controls were compared. The genotype distribution of the -765G > C polymorphism was not different between the patients with LI or LA and the control group. The 1195A allele carriers was identified independently to be related with LA (adjusted OR = 1.41, 95 % confidence interval (CI) = 1.09-2.10, P = 0.03) but not associated with LI. The linkage disequilibrium analysis showed that -1195G > A and -765G > C SNPs are moderate linkage disequilibrium in this study population (D' = 0.70, r(2) = 0.16). Compared with G-1195-G-765 haplotype, the haplotype of A-1195-G-765 showed significantly increased the risk of LA (OR = 1.24, 95 % CI = 1.10-1.55, P = 0.04) but not LI. In conclusion, we found that -1195G > A polymorphism and A-1195-G-765 haplotype of COX-2 were associated with susceptibility to LA in a Chinese population.

The haplotype of the TGFß1 gene associated with cerebral infarction in Chinese.

BACKGROUND: Transforming growth factor beta1 (TGFß1) is a multifunctional cytokine involved in inflammation and pathogenesis of atherosclerosis. The aim of the present study was to investigate the relationship between human TGFß1 gene +869T>C (rs1800470), -509C>T (rs1800469) single nucleotide polymorphisms (SNPs) and haplotypes and cerebral infarction (CI) in a Chinese population. METHODS: The genetic association study was performed in 450 Chinese patients (306 male and 144 female) with CI and 450 control subjects (326 male and 124 female). TGFß1 gene +869T>C and -509C>T polymorphisms were identified with amplification refractory mutation system polymerase chain reaction and DNA sequencing method. RESULTS: The individual SNPs analysis showed the +869T and -509C in an additive model (+869T vs +869C; -509 C vs T), +869TT genotype in a recessive model (TT vs TC+CC) and 509CC genotype in a dominant model (CC+ CT vs TT) were identified to be related to CI (P<0.05). +869T>C and -509C>T SNPs were in strong linkage disequilibrium (d'=0.87, R2=0.75). Haplotype analysis showed that +869C/-509T haplotype was associated with a significant decreased risk of CI (OR= 0.86, 95%CI, 0.70-0.92; P=0.007). Furthermore,+869T/-509C haplotype was associated with a significant increased risk of CI (OR=1.31, 95%CI, 1.10-2.03; P=0.019). CONCLUSIONS: The results of this study indicate that polymorphisms and the haplotypes in the TGFß1 gene might be genetic markers for CI in the Chinese population.