Evidence mapPaperPMID 40183010Full record

SynthesisFrontiers in neurology2025

Association between methylenetetrahydrofolate reductase C677T polymorphism and cerebral small vessel disease: a systematic review and meta-analysis.

Hao-Tao Zheng, Wen-Wen Lai, Jian-Jun Wang, Fan-Xin Kong, Hao-Bin Cai, Song-Jun Lin, Xu Wang, Dong-Bin Cai, Min Pi, Xiu-de Qin

Abstract readSystematic Review
In one paragraph

Synthesis in Frontiers in neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Hao-Tao Zheng *Department of Encephalopathy and Phycology, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China.
Wen-Wen Lai *Department of Child Healthcare, Luohu District Maternal and Child Health Hospital, Shenzhen, China.
Jian-Jun WangDepartment of Encephalopathy and Phycology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China.
Fan-Xin KongDepartment of Encephalopathy and Phycology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China.
Hao-Bin CaiDepartment of Encephalopathy and Phycology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China.
Song-Jun LinDepartment of Encephalopathy and Phycology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China.
Xu WangDepartment of Encephalopathy and Phycology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China.
Dong-Bin CaiDepartment of Encephalopathy and Phycology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China.
Min PiDepartment of Preventive Healthcare and Hospital Infection Management, Shenzhen Hospital of Traditional Chinese Medicine, Shenzhen, China.
Xiu-de QinDepartment of Encephalopathy and Phycology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Objective: This systematic review and meta-analysis aimed to evaluate the association between the methylenetetrahydrofolate reductase (5,10-methylenetetrahydrofolate reductase, MTHFR) cytosine (C)677thymine (T) polymorphism and cerebral small vessel disease (CSVD), addressing potential sources of heterogeneity and publication bias. Methods: An extensive search of databases, including PubMed, the Excerpta Medical Database, and The Cochrane Database of Systematic Reviews, was conducted to identify studies assessing the prevalence of the MTHFR C677T variant associated with CSVD subtypes in humans. Random or fixed effects models were used to accommodate heterogeneity across the study results. Odds ratios (ORs) and weighted mean differences with 95% confidence intervals (CIs) were used for pooled analyses of the relationships between the MTHFR C677T variant associated and CSVD subtypes. Subgroup analyses and assessments of publication bias were performed using Stata software. Results: Nineteen studies involving 12,441 participants were included. Significant associations were observed across all genetic models: recessive (OR = 1.33; 95%CI = 1.16, 1.52), dominant (OR = 1.25; 95%CI = 1.14, 1.37), allelic (OR = 1.24; 95%CI = 1.14, 1.35), TT vs. CC (OR = 1.42; 95%CI = 1.25, 1.61), and CT vs. CC (OR = 1.20; 95%CI = 1.09, 1.32). Subgroup analyses revealed stronger associations in CSVD-NOS. However, the trim-and-fill method indicated significant publication bias, with adjusted ORs becoming non-significant (recessive model: OR =1.10, 95% CI=0.81, 1.49). Heterogeneity was low to moderate across models ( Conclusion: This study highlights the significant association between MTHFR C677T genotyping and CSVD. Early assessment of MTHFR C677T genotyping during the clinical evaluation of elderly patients may improve patient management and reduce the adverse prognostic impact of the CSVD burden. However, further validation of these findings in large-scale, high-quality prospective studies is required. Systematic review registration: https://www.crd.york.ac.uk/prospero/; identifier: CRD42023339320.

Indexed as

cerebral small vessel diseaselacunar infarctionmeta-analysismicrobleedsMTHFR C677T polymorphismwhite matter hyperintensities

Identifiers

PMID40183010
PMCPMC11965132

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.