Related Experiment Video
Updated: Jun 3, 2025
09:42
A Fibrin-Enriched and tPA-Sensitive Photothrombotic Stroke Model
Published on: June 4, 2021
2.6K
Association Between Folate Metabolism Risk, Collateral Circulation, and Hemorrhagic Risk in Moyamoya Disease
Junsheng Li1,2, Qiheng He1,2, Chenglong Liu1,2
1Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No.119 Nan Si Huan Xi Road, Fengtai District, Beijing, China.
Translational Stroke Research
|January 8, 2025
Summary
Genetic variations in folate metabolism, specifically MTHFR and MTRR, impact moyamoya disease (MMD) hemorrhage risk. High folate metabolism risk is linked to decreased hemorrhagic risk, poor collateral circulation, and elevated homocysteine levels.
Area of Science:
- Genetics
- Vascular Biology
- Metabolic Disorders
Background:
- Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) gene polymorphisms influence folate metabolism and homocysteine levels, contributing to vascular disease risk.
- Moyamoya disease (MMD) is a cerebrovascular disorder characterized by progressive stenosis of intracranial arteries, leading to ischemic or hemorrhagic events.
Purpose of the Study:
- To investigate the association between genetic variations in folate metabolism (MTHFR, MTRR) and hemorrhagic risk in patients with moyamoya disease (MMD).
- To explore the relationship between folate metabolism risk, collateral circulation, and periventricular anastomosis (PA) in MMD.
- To elucidate the in vitro mechanisms underlying the impact of homocysteine on endothelial cells.
Main Methods:
- Prospective study involving 350 MMD patients with MTHFR and MTRR genotype data.
- Classification of folate metabolism risk based on genotype configurations and division of patients into non-hemorrhagic and hemorrhagic groups.
- Analysis of associations between folate metabolism risk, hemorrhagic risk, collateral circulation, PA, and homocysteine levels; in vitro experiments on human brain endothelial cells (HBMECs).
Main Results:
- TT genotype and T allele in MTHFR C677T were associated with lower hemorrhagic risk; AC genotype and C allele in MTHFR A1298C were linked to higher hemorrhagic risk.
- Patients with high folate metabolism risk showed a significantly decreased risk of hemorrhage compared to those with low risk.
- High folate metabolism risk correlated with poor collateral circulation, PA dilation, and elevated homocysteine; in vitro, elevated homocysteine inhibited HBMEC proliferation, migration, and tube formation.
Conclusions:
- Genetic variations in folate metabolism are significantly associated with hemorrhagic risk in moyamoya disease.
- High folate metabolism risk is unexpectedly linked to a reduced risk of hemorrhage in MMD, potentially mediated by homocysteine's effects on cerebral vasculature.
- Findings suggest a complex interplay between folate metabolism, homocysteine, and cerebrovascular integrity in MMD pathogenesis.
