Title:The U-shaped Relationship Between Serum Methylene Tetrahydrofolate Reductase and Large-artery Atherosclerotic Stroke
Volume: 16
Issue: 1
Author(s): Yan He, Zhengbao Zhu, Daoxia Guo, Huan Zhang, Xiaowei Zheng, Nimei Zeng, Qiu Zhang, Hao Peng, Chongke Zhong, Aili Wang, Tan Xu, Jianhua Jin, Yonghong Zhang*Jiang He
Affiliation:
- Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou,China
Keywords:
Methylene tetrahydrofolate reductase, large-artery atherosclerotic stroke, biomarkers, case-control study ischemic
stroke, hypertension, gene polymorphisms.
Abstract:
Background: Methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms
have been reported to be associated with ischemic stroke. However, the association between serum
MTHFR level and ischemic stroke has not yet been studied. We aimed to examine the association
between them in patients with large-artery atherosclerotic stroke and community-based healthy
controls.
Methods: This study includes three hundred ninety-five patients with large-artery atherosclerotic
stroke from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) and 395 age- and
sex-matched healthy controls from Chinese communities. Serum MTHFR concentrations were examined
and some conventional risk factors of stroke were collected. The association between serum
MTHFR and large-artery atherosclerotic stroke was evaluated.
Results: A U-shaped association of serum MTHFR level with large-artery atherosclerotic stroke
was observed (p for nonlinearity =0.008). After multivariate adjustment, the odds ratios (95%
confidence intervals) of large-artery atherosclerotic stroke associated with the first, second, fourth,
and fifth quintiles of MTHFR were 5.62 (1.10-28.87), 2.13 (0.51-8.99), 1.08 (0.21-5.56), and 2.31
(0.57-9.34), respectively, compared with the third quintiles of MTHFR. Adding MTHFR quintiles
to a model containing conventional risk factors improved the predictive power for large-artery
atherosclerotic stroke (continuous net reclassification improvement=63.78%, p<0.001; categorical
net reclassification improvement=2.54%, p=0.012).
Conclusion: There is a significant U-shaped relationship between serum MTHFR levels and largeartery
atherosclerotic stroke. Our findings raise the possibility that serum MTHFR may have a potential
role in the pathogenesis of large-artery atherosclerotic stroke.
