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      MTHFR A1298C gene polymorphism on stroke risk: an updated meta-analysis

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          Abstract

          Background

          Previous studies have shown the effect of MTHFR A1298C gene polymorphism on stroke risk. But the results of published studies remained inconclusive and controversial. So we conducted a meta-analysis to accurately estimate the potential association between MTHFR A1298C gene polymorphism and stroke susceptibility.

          Methods

          A systematic literature search on Embase, Pubmed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI) and WanFang electronic database identified 40 articles including 5725 cases and 8655 controls. Strength of association was evaluated by pooled odds ratio (OR), 95% confidence interval (CI) and p value. Funnel plots and Begger’s regression test were applied for testing the publication bias. Statistical analysis of all data was performed by Stata 12.0.

          Results

          The meta-analysis results indicated a significant relationship between MTHFR gene A1298C polymorphisms and stoke risk under the C allelic genetic model (OR = 1.19, 95%CI = 1.07–1.32, p = 0.001), dominant genetic model (OR = 1.19, 95%CI = 1.06–1.33, p = 0.004) and recessive genetic model (OR = 1.43, 95%CI =1.15–1.77, p = 0.001). In subgroup analysis, we discovered obvious correlation in three genetic model of Asian, stroke type, adult by ethnicity, population, stroke type, source of control and case size. Additionally, in studies of control from hospital and case size equal 100, obvious correlation was also found in the three genetic model.

          Conclusions

          Our meta-analysis results indicated that there was evidence to support the correlation between M THFR A1298C polymorphism and stroke susceptibility, especially in adults and ischemic stroke.

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          Most cited references44

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          Quantifying heterogeneity in a meta-analysis.

          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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            Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses.

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              A common mutation in the methylenetetrahydrofolate reductase gene is associated with an accumulation of formylated tetrahydrofolates in red blood cells.

              A common mutation (C677T) in the gene encoding for methylenetetrahydrofolate reductase (MTHFR) (5-methyltetrahydrofolate:(acceptor) oxidoreductase, EC 1.7.99.5), a key regulatory enzyme in one-carbon metabolism, results in a thermolabile variant of the MTHFR enzyme with reduced activity in vitro. In the present study we used a chromatographic method for folate analysis to test the hypothesis that this mutation would be associated with altered distribution of red blood cell (RBC) folates. An alteration was found as manifested by the presence of formylated tetrahydrofolate polyglutamates in addition to methylated derivatives in the RBCs from homozygous mutant individuals. 5-Methyltetrahydrofolate polyglutamates were the only folate form found in RBCs from individuals with the wild-type genotype. Existence of formylated folates in RBCs only from individuals with the thermolabile MTHFR is consistent with the hypothesis that there is in vivo impairment in the activity of the thermolabile variant of MTHFR and that this impairment results in an altered distribution of RBC folates.
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                Author and article information

                Contributors
                wanggesheng0623@163.com
                Journal
                Genes Environ
                Genes Environ
                Genes and Environment
                BioMed Central (London )
                1880-7046
                1880-7062
                25 September 2021
                25 September 2021
                2021
                : 43
                : 40
                Affiliations
                [1 ]GRID grid.24695.3c, ISNI 0000 0001 1431 9176, The Third department of Encephalopathy, , Dongfang Hospital Beijing University of Chinese Medicine, ; No. 6, Area 1, Fangxing Garden Fangzhuang, Fengtai District, Beijing, 100078 China
                [2 ]GRID grid.414252.4, ISNI 0000 0004 1761 8894, Department of Neurology, Chinese PLA General Hospital, ; Beijing, 100039 China
                Article
                208
                10.1186/s41021-021-00208-z
                8467014
                34563265
                b955f430-33ad-4bdb-a4df-0e3ea58bb19f
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 14 April 2021
                : 30 May 2021
                Categories
                Research
                Custom metadata
                © The Author(s) 2021

                mthfr a1298c,polymorphism,stroke,meta-analysis
                mthfr a1298c, polymorphism, stroke, meta-analysis

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