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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.

Author information

1
Department of Neurology, The Second People's Hospital of Hefei City, Hefei, China; Rambam Hospital, Rambam Health Care Campus, Haifa, Israel.
2
Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China; Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
3
School of Clinical Medicine, Bengbu Medical College, Bengbu, China.
4
Department of Neurology, The Second People's Hospital of Hefei City, Hefei, China.
5
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: qunsen6163@163.com.

Abstract

OBJECTIVE:

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.

METHODS:

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.

RESULTS:

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)).

CONCLUSIONS:

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.

KEYWORDS:

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

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