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.

Background:Transforming growth factor beta1 (TGFβ1) is a multifunctional cytokine involved in inflammation and pathogenesis of atherosclerosis. The aim of the present study was to investigate the relationship between human TGFβ1 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). TGFβ1 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 TGFβ1 gene might be genetic markers for CI in the Chinese population.

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.