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The U-shaped relationship between serum methylene tetrahydrofolate reductase and large-artery atherosclerotic stroke

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* and Jiang He  

Abstract:


Introduction: Methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms has been suggested 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: 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 communities in China were studied. Serum MTHFR 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% conīŦdence interval) 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, comparted with the third quintiles of MTHFR. Adding MTHFR quintiles to a model containing conventional risk factors improved the reclassification power for large-artery atherosclerotic stroke (continuous net reclassification improvement=63.78%, p<0.001; categorical net reclassification improvement=2.54%, p=0.012).

Conclusions: There is a significant U-shaped relationship between serum MTHFR levels and large-artery atherosclerotic stroke. Our findings raise the possibility that serum MTHFR may have a potential role in large-artery atherosclerotic stroke.

Keywords:

Methylene tetrahydrofolate reductase, large-artery atherosclerotic stroke, biomarkers, case-control study

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, 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, 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, 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, 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, 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, Center for Disease Prevention and Control of Gusu District, Suzhou, 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, 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, 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, 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, Center for Disease Prevention and Control of Gusu District, Suzhou, 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, Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA



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