Promoter polymorphism of <i>TNF‑α</i> (rs1800629) is associated with ischemic stroke susceptibility in a southern Thai population
Kornyok Kamdee, Nitirat Panadsako, Onchuma Mueangson, Manit Nuinoon, Penchom Janwan, Wasinee Poonsawat, Pongphan Pongpanitanont, Nakarin Kitkumthorn, Jirapan Thongsroy, Warangkana Chunglok
Abstract
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 <em>IL‑6</em>‑174G/C (rs1800795) and<em> TNF‑α</em>‑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 <em>IL‑6</em>‑174G/C and <em>TNF‑α</em>‑308G/A polymorphisms with IS. Genomic DNA from 200 patients with IS and 200 controls were genotyped for <em>IL‑6</em>‑174G/C and <em>TNF‑α</em>‑308G/A polymorphisms using TaqMan™ SNP genotyping and quantitative PCR‑high resolution melting analysis, respectively. It was found that the <em>TNF‑α</em>‑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 <em>TNF‑α</em>‑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 <em>IL‑6</em>‑174G/C and the risk of IS development. The interaction study demonstrated that <em>IL‑6</em>‑174 GG and <em>TNF‑α</em>‑308 GG genotypes enhanced IS susceptibility when combined with hypertension, hyperlipidemia and alcohol consumption. Hypertensive and hyperlipidemic subjects with the <em>TNF‑α</em>‑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 <em>IL‑6</em>‑174 GC genotype was associated with higher IL‑6 levels in the control group. Collectively, the present results highlight the utility of the <em>TNF‑α</em>‑308G/A polymorphism as a predictive genetic risk factor for development of IS.