TY - JOUR
T1 - Homocysteine and Stroke Risk
T2 - Modifying Effect of Methylenetetrahydrofolate Reductase C677T Polymorphism and Folic Acid Intervention
AU - Zhao, Min
AU - Wang, Xiaobin
AU - He, Mingli
AU - Qin, Xianhui
AU - Tang, Genfu
AU - Huo, Yong
AU - Li, Jianping
AU - Fu, Jia
AU - Huang, Xiao
AU - Cheng, Xiaoshu
AU - Wang, Binyan
AU - Hou, Fan Fan
AU - Sun, Ningling
AU - Cai, Yefeng
N1 - Funding Information:
The study was supported by National Science and Technology Major Projects Specialized for "Precision Medicine Research" during the 13th Five-Year Plan Period (2016YFC0903100); Projects of National Natural Science Foundation of China (grants 81473052 and 81402735); the Science, Technology and Innovation Committee of Shenzhen (JCYL20130401162636527); the Department of Development and Reform, Shenzhen Municipal Government (grant SFG 20201744); the Special Project on the Integration of Industry, Education and Research of Guangdong Province (2011A091000031); Science and Technology Planning Project of Guangdong Province, China (grant No. 2014B090904040), Science and Technology Planning Project of Guangdong Province, China (grant No. 201604020003), and research grants from China Postdoctoral Science Foundation (grant No. 2016M592513).
Publisher Copyright:
© 2017 American Heart Association, Inc.
PY - 2017/5/1
Y1 - 2017/5/1
N2 - 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.
AB - 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.
KW - folic acid
KW - genetic
KW - homocysteine
KW - methylenetetrahydrofolate reductase (MTHFR)
KW - polymorphism
KW - stroke
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UR - http://www.scopus.com/inward/citedby.url?scp=85016614682&partnerID=8YFLogxK
U2 - 10.1161/STROKEAHA.116.015324
DO - 10.1161/STROKEAHA.116.015324
M3 - Article
C2 - 28360116
AN - SCOPUS:85016614682
SN - 0039-2499
VL - 48
SP - 1183
EP - 1190
JO - Stroke
JF - Stroke
IS - 5
ER -