Polymorphism of tumor necrosis factor alpha (TNF-alpha) gene promoter, circulating TNF-alpha level, and cardiovascular risk factor for ischemic stroke

• Published in: Journal of neuroinflammation Vol. 9; no. 1; p. 235
• Main Authors: Cui, Guanglin, Wang, Haoran, Li, Rui, Zhang, Lina, Li, Zongzhe, Wang, Yan, Hui, Rutai, Ding, Hu, Wen Wang, Dao
• Format: Journal Article
• Language: English
• Published: London BioMed Central 10.10.2012; BioMed Central Ltd; BMC
• Subjects: Adult; Aged; Biomedical and Life Sciences; Biomedicine; Biotechnology industry; Cardiovascular disease; Cardiovascular diseases; Cardiovascular risk factors; Cardiovascular system; Case-Control Studies; Cell Line, Transformed; Central nervous system; Cohort Studies; Cytokines; Data processing; Female; Function study; Gene Frequency; Gene polymorphism; Genes; Genetic aspects; Genetic Linkage; Genetic polymorphisms; Genetic Predisposition to Disease; Genetic research; Genetics; Genotype; Health risks; Hospitals; Humans; Immunology; Inflammation; Ischemia; Ischemia - complications; Male; Medical research; Medicine, Experimental; Meta-analysis; Middle Aged; Mutation; Necrosis; Neurobiology; Neurology; Neurosciences; Polymorphism, Single Nucleotide; Promoter Regions, Genetic - genetics; Promoters; Promoters (Genetics); Public health; Reviews; Risk Factors; Stroke; Stroke (Disease); Stroke - blood; Stroke - epidemiology; Stroke - etiology; Stroke - genetics; Studies; Transfection; Tumor necrosis factor; Tumor necrosis factor alpha (TNF-α); Tumor necrosis factor- alpha; Tumor Necrosis Factor-alpha - blood; Tumor Necrosis Factor-alpha - genetics; Tumors; United States; Genetics; Tumor necrosis factor alpha (TNF-α); Cardiovascular risk factors; Function study
• ISSN: 1742-2094; 1742-2094
• DOI: 10.1186/1742-2094-9-235

Background Tumor necrosis factor-α (TNF-α) is one of the most typical pro-inflammatory cytokines with both beneficial and destructive properties for the central nervous system. Increasing evidences have demonstrated the important role of TNF-α in the development of ischemic stroke, but studies examining the possible association with stroke or direct functional effects of polymorphisms in TNF-α have been contradictory. Findings In this study, a 2-kb length of the proximal promoter of the TNF-α was screened and four polymorphisms were investigated in the case–control study. Our data confirmed the association between -308G/A variant with stroke in 1,388 stroke patients and 1,027 controls and replicated in an independent population of 961 stroke patients and 821 controls (odds ratio (OR) = 1.34, 95% confidence interval (CI) =1.02 to 1.77 and OR = 1.56, 95% CI = 1.09 to 2.23, respectively). To reconcile the association between polymorphisms and stroke and to give a comprehensive picture of the genetic architecture of this important gene, we performed a meta-analysis of 15 published studies in an Asian population. Our results demonstrated an association between rs1800629 and ischemic stroke (OR = 1.43, 95% CI = 1.21 to 1.69). Another meta-analysis results of 14 studies demonstrated that ischemic stroke patients have higher serum TNF-α level than the control subjects (standardized mean difference (SMD) = 2.33, 95% CI = 1.85 to 2.81). In vitro evaluation of potential interaction between variants of the TNF-α gene (−308G/A, -857C/T, and -1031T/C) demonstrated that these three polymorphisms could interact together to determine the overall activity of the TNF-α gene. Conclusions These findings strongly implicate the involvement of TNF-α in the pathogenesis of stroke.