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      Association between TNF-a promoter -308G/A polymorphism and essential hypertension in the Asian population: A meta-analysis

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          Abstract

          Objective:

          The results of studies on the association between tumor necrosis factor-a -308G/A (TNF-a -308G/A) polymorphism, and susceptibility to essential hypertension are controversial. To derive a more precise estimation, we conducted a meta-analysis of all similar articles.

          Methods:

          The summary effect odds ratios and 95% confidence intervals were obtained. Funnel plots and Egger’s test were used to estimate publication bias, and heterogeneity was assessed by the chi-square-based Q-test and I 2 test.

          Results:

          Nine studies (with 1437 cases and 1487 controls) were included. In the overall analysis, the combined results showed that there were significant differences in genotype distribution between essential hypertension cases and controls, AA+GA versus GG (OR = 1.53, 95% CI: 1.25–1.88, p < 0.00001). In the stratified analysis by country, we found that essential hypertension cases had a significantly higher frequency of AA+GA versus GG (OR = 1.47, 95% CI: 1.18–1.81, p = 0.0004) than control in the Asian population.

          Conclusions:

          This meta-analysis supports previous findings that TNF-a -308G/A polymorphism may increase the risk of essential hypertension, at least in the Asian population.

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          Most cited references31

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          Quantifying heterogeneity in a meta-analysis.

          Julian P T Higgins, Simon G Thompson (2002)
          The extent of heterogeneity in a meta-analysis partly determines the difficulty in drawing overall conclusions. This extent may be measured by estimating a between-study variance, but interpretation is then specific to a particular treatment effect metric. A test for the existence of heterogeneity exists, but depends on the number of studies in the meta-analysis. We develop measures of the impact of heterogeneity on a meta-analysis, from mathematical criteria, that are independent of the number of studies and the treatment effect metric. We derive and propose three suitable statistics: H is the square root of the chi2 heterogeneity statistic divided by its degrees of freedom; R is the ratio of the standard error of the underlying mean from a random effects meta-analysis to the standard error of a fixed effect meta-analytic estimate, and I2 is a transformation of (H) that describes the proportion of total variation in study estimates that is due to heterogeneity. We discuss interpretation, interval estimates and other properties of these measures and examine them in five example data sets showing different amounts of heterogeneity. We conclude that H and I2, which can usually be calculated for published meta-analyses, are particularly useful summaries of the impact of heterogeneity. One or both should be presented in published meta-analyses in preference to the test for heterogeneity. Copyright 2002 John Wiley & Sons, Ltd.
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            Bias in meta-analysis detected by a simple, graphical test.

            M. Egger, G Davey Smith, M. Schneider … (1997)
            Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews. Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision. In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias. A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution.
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              Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation.

              A Wilson, J A Symons, T McDowell … (1997)
              Tumor necrosis factor alpha (TNF alpha) is a potent immunomodulator and proinflammatory cytokine that has been implicated in the pathogenesis of autoimmune and infectious diseases. For example, plasma levels of TNF alpha are positively correlated with severity and mortality in malaria and leishmaniasis. We have previously described a polymorphism at -308 in the TNF alpha promoter and shown that the rare allele, TNF2, lies on the extended haplotype HLA-A1-B8-DR3-DQ2, which is associated with autoimmunity and high TNF alpha production. Homozygosity for TNF2 carries a sevenfold increased risk of death from cerebral malaria. Here we demonstrate, with reporter genes under the control of the two allelic TNF promoters, that TNF2 is a much stronger transcriptional activator than the common allele (TNF1) in a human B cell line. Footprint analysis using DNase I and B cell nuclear extract showed the generation of a hypersensitive site at -308 and an adjacent area of protection. There was no difference in affinity of the DNA-binding protein(s) between the two alleles. These results show that this polymorphism has direct effects on TNF alpha gene regulation and may be responsible for the association of TNF2 with high TNF alpha phenotype and more severe disease in infections such as malaria and leishmaniasis.
              Article 0 comments Cited 228 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Renin Angiotensin Aldosterone Syst
                Journal ID (iso-abbrev): J Renin Angiotensin Aldosterone Syst
                Journal ID (publisher-id): JRA
                Journal ID (hwp): spjra
                Title: Journal of the Renin-Angiotensin-Aldosterone System: JRAAS
                Publisher: SAGE Publications (Sage UK: London, England )
                ISSN (Print): 1470-3203
                ISSN (Electronic): 1752-8976
                Publication date (Electronic): 19 December 2017
                Publication date Collection: Oct-Dec 2017
                Volume: 18
                Issue: 4
                Electronic Location Identifier: 1470320317741066
                Affiliations
                [1-1470320317741066]Department of Preventive Medicine, Wannan Medical College, China
                Author notes
                [*]Ying-shui Yao, Department of Preventive Medicine, Wannan Medical College, 241001 Wuhu, Anhui, China. Email: yingshuiyao@ 123456163.com
                Article
                Publisher ID: 10.1177_1470320317741066
                DOI: 10.1177/1470320317741066
                PMC ID: 5843847
                PubMed ID: 29258412
                SO-VID: ee689d4e-1bc6-4d78-ad2f-e9664c76d689
                Copyright © © The Author(s) 2017
                License:

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                Date received : 7 September 2016
                Date accepted : 12 October 2017
                Funding
                Funded by: National Natural Science Foundation of China, FundRef https://doi.org/10.13039/501100001809;
                Award ID: 81072367
                Categories
                Subject: Original Article
                Custom metadata
                cover-date October-December 2017

                Keywords: essential hypertension,gene,polymorphism,tnf-a -308g/a,meta-analysis
                Data availability:
                Keywords: essential hypertension, gene, polymorphism, tnf-a -308g/a, meta-analysis

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