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Review
. 2016 Apr;3(3-4):217-28.
doi: 10.1159/000443770. Epub 2016 Feb 17.

Association between Tumor Necrosis Factor-α (-238G/A and -308G/A) Gene Polymorphisms and Risk of Ischemic Stroke: A Meta-Analysis

Pradeep Kumar  1 , Shubham Misra  1 , Amit Kumar  1 , Awadh Kishor Pandit  1 , Kamalesh Chakravarty  1 , Kameshwar Prasad  1
Affiliations
Review

Association between Tumor Necrosis Factor-α (-238G/A and -308G/A) Gene Polymorphisms and Risk of Ischemic Stroke: A Meta-Analysis

Pradeep Kumar et al. Pulse (Basel). 2016 Apr.

Abstract

Tumor necrosis factor-α (TNF-α) is a proinflammatory pleiotropic cytokine which may contribute to the initiation and progression of ischemic stroke (IS). Thus far, numerous studies have been performed to examine the association between -238G/A (rs361525) and -308G/A (rs1800629) polymorphisms in the promoter regions of the TNF-α gene and susceptibility to IS, but results are still conflicting. The aim of this meta-analysis is to provide a relatively comprehensive account of the association between TNF-α -238G/A and -308G/A gene polymorphisms and susceptibility to IS. A literature search for eligible candidate gene studies published before April 20, 2015, was conducted in the PubMed, Medline, EMBASE and Google Scholar databases. The following combinations of main keywords were used: ('Tumor Necrosis Factor-Alpha' or 'TNF-α') and ('ischemic stroke' or 'cerebral infarction' or 'IS') and ('genetic polymorphism' or 'single nucleotide polymorphisms' or 'SNP'). Fixed- or random-effect models were used to estimate the pooled odds ratio (OR) and 95% confidence interval (CI). Meta-analysis was carried out by using RevMan 5.3 software. For TNF-α -238G/A gene polymorphism, 7 case-control studies with a total of 1,846 IS patients and 1,905 controls showed a significant association with susceptibility to IS under a dominant model (AA + GA vs. GG; OR, 1.40; 95% CI, 1.11-1.76; p value 0.004). For TNF-α -308G/A gene polymorphism, 16 case-control studies with a total of 5,651 IS patients and 5,792 controls showed a significant protective association with susceptibility to IS under a dominant model (AA + GA vs. GG; OR, 0.78, 95% CI, 0.63-0.97; p value 0.03). Our meta-analysis shows that TNF-α -238G/A gene polymorphism is more likely to be associated with the risk of IS in Caucasian populations as compared to Asian populations. However, TNF-α -308G/A gene polymorphism is more likely to be protective against IS in Asian populations as compared to Caucasian populations. Further large, well-designed prospective epidemiological studies are needed to confirm these findings.

Keywords: Cerebral infarction; Cytokines; Inflammatory gene; Ischemic stroke; Meta-analysis; Polymorphisms; Tumor necrosis factor-α.

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Figures

Fig. 1
Fig. 1
Flow diagram of the selection of studies and specific reasons for exclusion from the present meta-analysis.
Fig. 2
Fig. 2
Forest plot for association between TNF −238G/A polymorphism and IS risk under the dominant model.
Fig. 3
Fig. 3
Begg's funnel plot for publication bias for TNF −238G/A gene polymorphism.
Fig. 4
Fig. 4
Forest plot for association between TNF −308 G/A polymorphism and IS risk under the dominant (a), recessive (b) and co-dominant (c) models.
Fig. 4
Fig. 4
Forest plot for association between TNF −308 G/A polymorphism and IS risk under the dominant (a), recessive (b) and co-dominant (c) models.
Fig. 4
Fig. 4
Forest plot for association between TNF −308 G/A polymorphism and IS risk under the dominant (a), recessive (b) and co-dominant (c) models.
Fig. 5
Fig. 5
Begg's funnel plot for publication bias for TNF −308G/A gene polymorphism.
See this image and copyright information in PMC

References

    1. Feigin VL, Lawes CMM, Bennett DA, Barker-Collo SL, Parag V. Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review. Lancet Neurol. 2009;8:355–369. - PubMed
    1. Bevan S, Markus HS. Genetics of common polygenic ischaemic stroke: current understanding and future challenges. Stroke Res Treat. 2011:179061. - PMC - PubMed
    1. Kim SK, Kang SW, Kim DH, Yun DH, Chung J-H, Ban JY. Matrix metalloproteinase-3 gene polymorphisms are associated with ischemic stroke. J Interferon Cytokine Res Off J Int Soc Interferon Cytokine Res. 2012;32:81–86. - PubMed
    1. Jin R, Yang G, Li G. Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. J Leukoc Biol. 2010;87:779–789. - PMC - PubMed
    1. Carr FJ, McBride MW, Carswell HVO, Graham D, Strahorn P, Clark JS, et al. Genetic aspects of stroke: human and experimental studies. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab. 2002;22:767–773. - PubMed