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. 2022 Aug 3:13:829672.
doi: 10.3389/fgene.2022.829672. eCollection 2022.

A systematic review and meta-analysis expounding the relationship between methylene tetrahydrofolate reductase gene polymorphism and the risk of intracerebral hemorrhage among populations

Xue-Lun Zou  1   2   3 , Tian-Xing Yao  1 , Lu Deng  1 , Lei Chen  1 , Ye Li  1 , Le Zhang  1   2   3
Affiliations

A systematic review and meta-analysis expounding the relationship between methylene tetrahydrofolate reductase gene polymorphism and the risk of intracerebral hemorrhage among populations

Xue-Lun Zou et al. Front Genet. .

Abstract

Background: The relationship between methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphism with the risk of intracerebral hemorrhage (ICH) has remained to be controversial in recent years. This meta-analysis is aimed to confirm the association of these. Methods: Systematically searching the related studies from the PubMed, Embase, Cochrane Library, China national knowledge internet database from 1 January 1990 to 1 June 2022. The odd ratio (ORs) and 95% confidence interval (CIs) of gene-disease correlation in various gene models were calculated by fixed or random effect model of meta-analysis. We included 20 case-control studies in this meta-analysis with a total of 1,989 ICH patients and 4,032 health controls originated from Asian, Caucasian, and African populations. Results: The statistical analysis demonstrated the association of MTHFR C677T gene polymorphism with ICH in allele model [ORT VS. C = 1.20 (95%CI: 1.06-1.36)]; homozygote model [OR TT VS. CC = 1.50 (95%CI: 1.20-1.88)]; dominant model [OR CT+ TT VS. CC = 1.23 (95%CI: 1.03-1.48)] and recessive model [ORTT VS. CT+CC = 1.37 (95%CI: 1.17-1.60)]. Besides, we also found the relationship of MTHFR C677T gene polymorphism with Asian in four comparison model (ORT VS. C = 1.19.95%CI:1.09-1.37, ORTT VS. CC = 1.46.95%CI: 1.15-1.85, OR CT+ TT VS. CC = 1.25.95%CI: 1.01-1.54, ORTT VS. CT+CC = 1.34.95%CI: 1.54-1.17) and Caucasian in four comparison model (ORT VS. C = 1.90.95%CI: 1.22-2.97, ORTT VS. CC = 2.67.95%CI: 1.42-5.00, OR CT+ TT VS. CC = 1.56.95%CI: 1.05-2.32, ORTT VS. CT+CC = 2.25.95%CI: 1.46-4.00). But no statistically significant correlation between A1298C polymorphism and the occurrence of ICH was detected in four studies. Conclusion: MTHFR C677T gene polymorphism increases the risk of ICH in Asian and Caucasian populations but has no impact on the incidence in African communities. More importantly, the risk of ICH increases in TT genotype individuals in comparison to CT and CC genotype individuals in Asian and Caucasian populations.

Keywords: A1298C; C677T; gene polymorphism; intracerebral hemorrhage; meta-analysis; methylenetetrahydrofolate reductase.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flow diagram for the selection of studies in this meta-analysis. CNKI: China national knowledge internet.
FIGURE 2
FIGURE 2
Homozygote gene model (TT VS. CC) in Asians, Caucasians, and Africans.
FIGURE 3
FIGURE 3
Begg’s funnel plot of the relationship between MTHFR gene (C677T) polymorphism and intracerebral hemorrhage risk.
See this image and copyright information in PMC

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References

    1. Abidi O., Haissam M., Nahili H., El Azhari A. (2018). Methylenetetrahydrofolate reductase gene polymorphisms (C677T and A1298C) and hemorrhagic stroke in Moroccan patients. J. Stroke Cerebrovasc. Dis. 27 (7), 1837–1843. 10.1016/j.jstrokecerebrovasdis.2018.02.029 - DOI - PubMed
    1. Aléssio A. C., Santos C. X., Debbas V., Oliveira L. C., Haddad R., Annichino-Bizzacchi J. M., et al. (2011). Evaluation of mild hyperhomocysteinemia during the development of atherosclerosis in apolipoprotein E-deficient and normal mice. Exp. Mol. Pathol. 90 (1), 45–50. 10.1016/j.yexmp.2010.07.008 - DOI - PubMed
    1. An S. J., Kim T. J., Yoon B. W. (2017). Epidemiology, risk factors, and clinical features of intracerebral hemorrhage: An update. J. Stroke 19 (1), 3–10. 10.5853/jos.2016.00864 - DOI - PMC - PubMed
    1. Atadzhanov M., Mwaba M. H., Mukomena P. N., Lakhi S., Rayaprolu S., Ross O. A., et al. (2013). Association of the APOE, MTHFR and ACE genes polymorphisms and stroke in Zambian patients. Neurol. Int. 5 (4), e20. 10.4081/ni.2013.e20 - DOI - PMC - PubMed
    1. Chen Y. C., Chang K. H., Chen C. M. (2018). Genetic polymorphisms associated with spontaneous intracerebral hemorrhage. Int. J. Mol. Sci. 19 (12), 3879. 10.3390/ijms19123879 - DOI - PMC - PubMed

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