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Int Immunopharmacol. 2019 Oct;75:105827. doi: 10.1016/j.intimp.2019.105827. Epub 2019 Aug 24.

Gene polymorphisms and circulating levels of the TNF-alpha are associated with ischemic stroke: A meta-analysis based on 19,873 individuals.

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Department of Neurology, The Second People's Hospital of Hefei City, Hefei, China; Rambam Hospital, Rambam Health Care Campus, Haifa, Israel.
Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China; Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
School of Clinical Medicine, Bengbu Medical College, Bengbu, China.
Department of Neurology, The Second People's Hospital of Hefei City, Hefei, China.
Stroke Center & Department of Neurology, First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. Electronic address:



Numerous studies have investigated associations of gene polymorphisms and circulating levels of TNF-α with ischemic stroke (IS), but the results were controversial. The aims of this study were to systematically evaluate these associations.


Relevant publications were retrieved by searching databases. Odds ratios (ORs) and standard mean differences (SMDs) with 95% confidence intervals (95% CIs) were used to assess the association of the TNF-α gene and cytokine with IS, respectively. The Cochrane Q test and I2 statistic were used to test heterogeneity. Subgroup analysis and publication bias were performed.


25 and 9 articles examined the association of polymorphisms and levels of the TNF-α with IS risk, respectively. Rs1800629 polymorphism was associated with IS susceptibility (OR (95% CI) =0.82 (0.72, 0.95)), especially in Asians (OR (95% CI) =0.75 (0.63, 0.89)); and rs1800610 was associated with IS susceptibility in Asians patients (OR (95% CI) =1.54 (1.31, 1.80)). While rs361525, rs1799964 and rs1799724 polymorphisms were not associated with IS susceptibility. The TNF-α level was elevated in IS patients (SMD (95% CI) =0.65 (0.29, 1.01)) including Asians (SMD (95% CI) =1.26 (0.49, 2.03)) and Caucasians (SMD (95% CI) =0.26 (0.03, 0.49)). In addition, increased level occurred in patients' serum (SMD (95% CI) =0.54 (0.08, 1.01)).


Rs1800629 and rs1800610 polymorphisms were elucidated to be a protective factor for IS (especially in Asians) and a risk factor for Asians patients, respectively. The TNF-α level was elevated in IS, indicating that TNF-α plays an important role in the pathogenesis of IS and is a promising therapeutic target for IS.


Cytokine; Gene; Ischemic stroke; Polymorphism; Stroke; TNF-α

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