Association of MTHFR C677T polymorphism with risk of atherosclerotic cardiovascular diseases: a systematic review and meta-analysis
- 1Department of Emergency Medicine, Hangzhou Third People’s Hospital, 38 Xihu Avenue, Shangcheng District, Hangzhou, 310009 China
Abstract
Background: Although several meta-analyses have examined the association between MTHFR C677T and specific cardiovascular outcomes, a comprehensive evaluation focusing on atherosclerotic cardiovascular disease (ASCVD) as a unified outcome, incorporating recently published studies (January 2016–March 2026), remains limited.
Methods: Potential studies were selected from Embase, Web of Science, and PubMed databases. Pooled effect size was evaluated by odds ratios (ORs) with 95% confidence intervals (CIs) using random-effects models where significant heterogeneity was present.
Results: Twenty-three case-control studies (including 6693 patients and 7692 controls) from January 2016 to March 2026 were enrolled in this study. Significant heterogeneity was observed across models (I² > 50%, all phet < 0.001), and random-effects models were applied. MTHFR C677T was positively correlated to ASCVD risk under the dominant model (OR = 1.71, 95%CI = 1.35–2.16), the recessive model (OR = 1.73, 95%CI = 1.35–2.23), and the allelic model (OR = 1.55, 95%CI = 1.30–1.84). Supplementary genotype-specific comparisons also showed significant associations. Subgroup analysis identified a significant correlation in studies of East Asian and North African populations, younger individuals, and healthy controls. The association was significant in coronary artery disease (CAD) and ischemic stroke (IS) patients. Region, age, control type, and disease type are the sources of heterogeneity.
Conclusions: MTHFR C677T was positively correlated with ASCVD risk across multiple genetic models.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12872-026-06418-z.
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BibTeX
@article{yang2026association,
title = {{Association of MTHFR C677T polymorphism with risk of atherosclerotic cardiovascular diseases: a systematic review and meta-analysis}},
author = {Kai Yang and Aihua Huang and Xiaolin Wang and Yidan Zhou},
journal = {BMC Cardiovascular Disorders},
year = {2026},
month = aug,
doi = {10.1186/s12872-026-06418-z},
url = {https://doi.org/10.1186/s12872-026-06418-z},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Association of MTHFR C677T polymorphism with risk of atherosclerotic cardiovascular diseases: a systematic review and meta-analysis
AU - Kai Yang
AU - Aihua Huang
AU - Xiaolin Wang
AU - Yidan Zhou
PY - 2026
DA - 2026/08/01
JO - BMC Cardiovascular Disorders
DO - 10.1186/s12872-026-06418-z
UR - https://doi.org/10.1186/s12872-026-06418-z
AB - Background: Although several meta-analyses have examined the association between MTHFR C677T and specific cardiovascular outcomes, a comprehensive evaluation focusing on atherosclerotic cardiovascular disease (ASCVD) as a unified outcome, incorporating recently published studies (January 2016–March 2026), remains limited. Methods: Potential studies were selected from Embase, Web of Science, and PubMed databases. Pooled effect size was evaluated by odds ratios (ORs) with 95% confidence intervals (CIs) using random-effects models where significant heterogeneity was present. Results: Twenty-three case-control studies (including 6693 patients and 7692 controls) from January 2016 to March 2026 were enrolled in this study. Significant heterogeneity was observed across models (I² > 50%, all phet < 0.001), and random-effects models were applied. MTHFR C677T was positively correlated to ASCVD risk under the dominant model (OR = 1.71, 95%CI = 1.35–2.16), the recessive model (OR = 1.73, 95%CI = 1.35–2.23), and the allelic model (OR = 1.55, 95%CI = 1.30–1.84). Supplementary genotype-specific comparisons also showed significant associations. Subgroup analysis identified a significant correlation in studies of East Asian and North African populations, younger individuals, and healthy controls. The association was significant in coronary artery disease (CAD) and ischemic stroke (IS) patients. Region, age, control type, and disease type are the sources of heterogeneity. Conclusions: MTHFR C677T was positively correlated with ASCVD risk across multiple genetic models. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12872-026-06418-z.
SN - 1471-2261
ER -