Promoter polymorphism of TNF-α (rs1800629) is associated with ischemic stroke susceptibility in a southern Thai population

Stroke represents the leading cause of disability and mortality amongst the elderly worldwide. Multiple risk factors, including both genetic and non-genetic components, as well as their interactions, are proposed as etiological factors involved in the development of ischemic stroke (IS). Promoter polymorphisms of the IL-6-174G/C (rs1800795) and TNF-alpha-308G/A (rs1800629) genes have been considered as predictive risk factors of IS; however, these have not yet been evaluated in a Thai population. The aims of this study were to investigate the association of IL-6-174G/C and TNF-alpha-308G/A polymorphisms with IS. Genomic DNA from 200 patients with IS and 200 controls were genotyped for IL-6-174G/C and TNF-alpha-308G/A polymorphisms using TaqMan (TM) SNP genotyping and quantitative PCR-high resolution melting analysis, respectively. It was found that the TNF-alpha-308 A allele was significantly associated with an increased risk of IS development compared with the G allele [odds ratio (OR)=2.044; 95% CI=1.154-3.620; P=0.014]. Moreover, the IS risk was significantly higher in the presence of TNF-alpha-308 GA or AA genotypes compared with that in the presence of GG genotypes with a dominant inheritance (OR=1.971; 95% CI=1.080-3.599; P=0.027). However, there was no association between IL-6-174G/C and the risk of IS development. The interaction study demonstrated that IL-6-174 GG and TNF-alpha-308 GG genotypes enhanced IS susceptibility when combined with hypertension, hyperlipidemia and alcohol consumption. Hypertensive and hyperlipidemic subjects with the TNF-alpha-308 GA and AA genotypes were more likely to develop IS compared with those who did not have these two conditions and had the GG genotype. In a matched study design (1:1), the IL-6-174 GC genotype was associated with higher IL-6 levels in the control group. Collectively, the present results highlight the utility of the TNF-alpha-308G/A polymorphism as a predictive genetic risk factor for development of IS.