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Review
. 2023 Jan 4:13:1021423.
doi: 10.3389/fgene.2022.1021423. eCollection 2022.

Association of methylenetetrahydrofolate reductase (MTHFR) rs1801133 (677C>T) gene polymorphism with ischemic stroke risk in different populations: An updated meta-analysis

Lili Zhao  1 , Tao Li  1 , Meijuan Dang  1 , Ye Li  1 , Hong Fan  1 , Qian Hao  2 , Dingli Song  3 , Jialiang Lu  1 , Ziwei Lu  1 , Yating Jian  1 , Heying Wang  1 , Xiaoya Wang  1 , Yulun Wu  1 , Guilian Zhang  1
Affiliations
Review

Association of methylenetetrahydrofolate reductase (MTHFR) rs1801133 (677C>T) gene polymorphism with ischemic stroke risk in different populations: An updated meta-analysis

Lili Zhao et al. Front Genet. .

Abstract

Background: Recently, increasing evidence has implicated methylenetetrahydrofolate reductase (MTHFR) gene mutation as a risk factor for ischemic stroke (IS) in the general population. However, studies have been inconclusive and lack evidence on specific populations. We aim to determine whether the rs1801133 (NC_000001.11 (MTHFR):g. 677C>T (p.Ala222Val) variant, we termed as MTHFR rs1801133 (677 C>T), is linked to an increased risk of IS in different age groups and ancestry groups. Methods: The literature relevant to our study was found by searching the PubMed, Cochrane Library, Web of Science, EMBASE, and CNKI databases. A random effect model analysis was used to calculate the pooled odds ratio (OR) and 95% confidence interval (CI) to evaluate any possible association. We conducted a subgroup analysis based on the age and ancestry groups of the included populations. Results: As of March 2022, 1,925 citations had been identified in electronic databases, of which 96 studies involving 34,814 subjects met our eligibility criteria. A strong link was found between IS and the MTHFR gene rs1801133 (677C>T) polymorphism in all genetic models [dominant genetic model (OR = 1.47; 95%CI = 1.33-1.61; p < 0.001), recessive genetic model (OR = 1.52; 95%CI = 1.36-1.71; p < 0.001), heterozygous model (OR = 1.36; 95%CI = 1.24-1.48; p < 0.001), homozygous model (OR = 1.82; 95%CI = 1.58-2.11; p < 0.001), and T allelic genetic model (OR = 1.37; 95%CI = 1.27-1.48; p < 0.001)]. Further subgroup analyses indicated that the MTHFR rs1801133 (677C>T) variant may increase the risk of IS in Asian, Hispanic, or Latin population, middle-aged, and elderly populations (p < 0.001). Conclusion: Our results implied that mutation of the T allele of MTHFR rs1801133 (677C>T) could be a risk factor for IS. A significant association was found among Asian, Hispanic, or Latin population, middle-aged, and elderly people.

Keywords: MTHFR rs1801133 (677C>T); ischemic stroke; meta-analysis; polymorphism; risk.

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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
Roles of methylenetetrahydrofolate reductase in homocysteine metabolism.
FIGURE 2
FIGURE 2
Flow chart of identification of eligible studies.
FIGURE 3
FIGURE 3
Funnel plots of the (A) dominant model; (B) recessive model; (C) heterozygous model; (D) homozygous model; and (E) allelic model.
See this image and copyright information in PMC

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