Association between 5,10-Methylenetetrahydrofolate Reductase C677T Gene Polymorphism and Risk of Ischemic Stroke: A Meta-analysis

Yanli Song; Bohong Li; Chunjuan Wang; Penglian Wang; Xiang Gao; Gaifen Liu

doi:10.1016/j.jstrokecerebrovasdis.2015.11.041

Association between 5,10-Methylenetetrahydrofolate Reductase C677T Gene Polymorphism and Risk of Ischemic Stroke: A Meta-analysis

J Stroke Cerebrovasc Dis. 2016 Mar;25(3):679-87. doi: 10.1016/j.jstrokecerebrovasdis.2015.11.041. Epub 2016 Jan 5.

Authors

Yanli Song¹, Bohong Li², Chunjuan Wang², Penglian Wang², Xiang Gao³, Gaifen Liu⁴

Affiliations

¹ Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China; Department of Neurology, Handan First Hospital, Handan, China.
² Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China.
³ Department of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State University. Electronic address: xxg14@psu.edu.
⁴ Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China. Electronic address: liugaifen1997@163.com.

PMID: 26776436
DOI: 10.1016/j.jstrokecerebrovasdis.2015.11.041

Abstract

Background: Hyperhomocysteinemia, a condition that is strongly determined by dietary intake of B vitamins, has been suggested to be an independent risk factor for ischemic stroke (IS). To test this hypothesis, we performed a meta-analysis to investigate the associations between 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, which plays a critical role in modulating plasma homocysteine concentrations, and IS risk.

Materials and methods: We searched case-control studies on the association between MTHFR C677T genetic polymorphism and susceptibility to IS through PubMed, Embase, and Medline databases from January 2000 up to October 2014. The random-effects model was employed because moderate heterogeneity across studies was observed, as assessed by I(2) statistic. Publication bias was estimated using funnel plot and Egger's regression test.

Results: A total of 22 case-control studies were included in the current meta-analysis. Significant associations between MTHFR C677T genetic polymorphism and IS were found under the dominant model (pooled odds ratio [OR] = 1.40, 95% confidence interval [CI]: 1.24-1.57), the recessive model (pooled OR = 1.37, 95% CI: 1.16-1.61), and the allele model (pooled OR = 1.29, 95% CI: 1.18-1.42).

Conclusions: The meta-analysis suggests that MTHFR C677T genetic polymorphism is significantly associated with susceptibility to IS, which provides evidence supporting hyperhomocysteinemia as a risk factor for stroke.

Keywords: Ischemic stroke; MTHFR; meta-analysis; polymorphism.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

5,10-Methylenetetrahydrofolate Reductase (FADH2) / genetics*
Brain Ischemia / complications
Case-Control Studies
Chi-Square Distribution
Databases, Bibliographic / statistics & numerical data
Female
Genetic Association Studies
Genetic Predisposition to Disease / genetics*
Humans
Male
Polymorphism, Single Nucleotide / genetics*
Stroke / etiology
Stroke / genetics*

Substances

5,10-Methylenetetrahydrofolate Reductase (FADH2)