Promoter polymorphism of TNF-α (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

doi:10.3892/br.2021.1454

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

Biomed Rep. 2021 Sep;15(3):78. doi: 10.3892/br.2021.1454. Epub 2021 Jul 23.

Affiliations

¹ School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand.
² Research Institute for Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand.
³ Department of Oral Biology, Faculty of Dentistry, Mahidol University, Bangkok 10400, Thailand.
⁴ School of Medicine, Walailak University, Nakhon Si Thammarat 80160, Thailand.
⁵ Food Technology and Innovation Research Center of Excellence, Institute of Research and Innovation, Walailak University, Nakhon Si Thammarat 80160, Thailand.

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 IL-6-174G/C (rs1800795) and TNF-α-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-α-308G/A polymorphisms with IS. Genomic DNA from 200 patients with IS and 200 controls were genotyped for IL-6-174G/C and TNF-α-308G/A polymorphisms using TaqMan™ SNP genotyping and quantitative PCR-high resolution melting analysis, respectively. It was found that the TNF-α-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-α-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-α-308 GG genotypes enhanced IS susceptibility when combined with hypertension, hyperlipidemia and alcohol consumption. Hypertensive and hyperlipidemic subjects with the TNF-α-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-α-308G/A polymorphism as a predictive genetic risk factor for development of IS.

Keywords: cytokine; inflammation; ischemic stroke; polymorphism.

Grants and funding

Funding: The present study was supported by the Walailak University Fund (grant no. WU-IRG-62-034), Thailand Science Research and Innovation Fund (grant no. WU-FF64102) and the Development and Promotion of Science and Technology Talents Project (DPST).