Homocysteine and Stroke Risk: Modifying Effect of Methylenetetrahydrofolate Reductase C677T Polymorphism and Folic Acid Intervention

Min Zhao, Xiaobin Wang, Mingli He, Xianhui Qin, Genfu Tang, Yong Huo, Jianping Li, Jia Fu, Xiao Huang, Xiaoshu Cheng, Binyan Wang, Fan Fan Hou, Ningling Sun, Yefeng Cai

Research output: Contribution to journalArticle

Abstract

Background and Purpose - Elevated blood homocysteine concentration increases the risk of stroke, especially among hypertensive individuals. Homocysteine is largely affected by the methylenetetrahydrofolate reductase C677T polymorphism and folate status. Among hypertensive patients, we aimed to test the hypothesis that the association between homocysteine and stroke can be modified by the methylenetetrahydrofolate reductase C677T polymorphism and folic acid intervention. Methods - We analyzed the data of 20 424 hypertensive adults enrolled in the China Stroke Primary Prevention Trial. The participants, first stratified by methylenetetrahydrofolate reductase genotype, were randomly assigned to receive double-blind treatments of 10-mg enalapril and 0.8-mg folic acid or 10-mg enalapril only. The participants were followed up for a median of 4.5 years. Results - In the control group, baseline log-transformed homocysteine was associated with an increased risk of first stroke among participants with the CC/CT genotype (hazard ratio, 3.1; 1.1-9.2), but not among participants with the TT genotype (hazard ratio, 0.7; 0.2-2.1), indicating a significant gene-homocysteine interaction (P=0.008). In the folic acid intervention group, homocysteine showed no significant effect on stroke regardless of genotype. Consistently, folic acid intervention significantly reduced stroke risk in participants with CC/CT genotypes and high homocysteine levels (tertile 3; hazard ratio, 0.73; 0.55-0.97). Conclusions - In Chinese hypertensive patients, the effect of homocysteine on the first stroke was significantly modified by the methylenetetrahydrofolate reductase C677T genotype and folic acid supplementation. Such information may help to more precisely predict stroke risk and develop folic acid interventions tailored to individual genetic background and nutritional status.

Original languageEnglish (US)
Pages (from-to)1183-1190
Number of pages8
JournalStroke
Volume48
Issue number5
DOIs
StatePublished - May 1 2017

Keywords

  • folic acid
  • genetic
  • homocysteine
  • methylenetetrahydrofolate reductase (MTHFR)
  • polymorphism
  • stroke

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

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    Zhao, M., Wang, X., He, M., Qin, X., Tang, G., Huo, Y., Li, J., Fu, J., Huang, X., Cheng, X., Wang, B., Hou, F. F., Sun, N., & Cai, Y. (2017). Homocysteine and Stroke Risk: Modifying Effect of Methylenetetrahydrofolate Reductase C677T Polymorphism and Folic Acid Intervention. Stroke, 48(5), 1183-1190. https://doi.org/10.1161/STROKEAHA.116.015324