TY - JOUR
T1 - Interaction of serum Vitamin B12and folate with MTHFR genotypes on risk of ischemic stroke
AU - Qin, Xianhui
AU - Spence, J. David
AU - Li, Jianping
AU - Zhang, Yan
AU - Li, Youbao
AU - Sun, Ningling
AU - Liang, Min
AU - Song, Yun
AU - Zhang, Yuanyuan
AU - Wang, Binyan
AU - Cheng, Xiaoshu
AU - Zhao, Lianyou
AU - Wang, Xiaobin
AU - Xu, Xiping
AU - Huo, Yong
N1 - Funding Information:
The study was supported by funding from the following: the National Key Research and Development Program (2016YFE0205400, 2018ZX09739, 2018ZX09301034003); the National Natural Science Foundation of China (81730019, 81973133); the Science and Technology Planning Project of Guangzhou, China (201707020010); the Science, Technology and Innovation Committee of Shenzhen (JSGG20170412155639040, GJHS20170314114526143); the Economic, Trade and Information Commission of Shenzhen Municipality (20170505161556110, 20170505160926390); and the Outstanding Youths Development Scheme of Nanfang Hospital, Southern Medical University (2017J009). The funders had no role in the design and/or conduct of the study (data collection, management, analysis, and interpretation); the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.
Funding Information:
X. Qin reports grants from the National Natural Science Foundation of China (81730019, 81973133) and the Outstanding Youths Development Scheme of Nanfang Hospital, Southern Medical University (2017J009). J. Spence is a consultant to Amgen and Orphan Technologies and has received lecture fees from Pfizer and Bristol-Myers-Squibb. J. Li, Y. Zhang, Y. Li, N. Sun, M. Liang, Y. Song, Y. Zhang, B. Wang, X. Cheng, L. Zhao, and X. Wang report no disclosures relevant to the manuscript. X. Xu reports grants from the National Key Research and Development Program (2016YFE0205400, 2018ZX09739, 2018ZX09301034003), the Science and Technology Planning Project of Guangzhou, China (201707020010), the Science, Technology and Innovation Committee of Shenzhen (JSGG20170412155639040, GJHS20170314114526143), and the Economic, Trade and Information Commission of Shenzhen Municipality (20170505161556110, 20170505160926390). Y. Huo reports no disclosures relevant to the manuscript. Go to Neurology. org/N for full disclosures.
Publisher Copyright:
© American Academy of Neurology.
PY - 2020/3/17
Y1 - 2020/3/17
N2 - ObjectiveWe evaluated the interaction of serum folate and vitamin B12 with methylenetetrahydrofolate reductase (MTHFR) C677T genotypes on the risk of first ischemic stroke and on the efficacy of folic acid treatment in prevention of first ischemic stroke.MethodsA total of 20,702 hypertensive adults were randomized to a double-blind treatment of daily enalapril 10 mg and folic acid 0.8 mg or enalapril 10 mg alone. Participants were followed up every 3 months.ResultsMedian values of folate and B12 concentrations at baseline were 8.1 ng/mL and 280.2 pmol/L, respectively. Over a median of 4.5 years, among those not receiving folic acid, participants with baseline serum B12 or serum folate above the median had a significantly lower risk of first ischemic stroke (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.57-0.96), especially in those with MTHFR 677 CC genotype (wild-type) (HR, 0.49; 95% CI, 0.31-0.78). Folic acid treatment significantly reduced the risk of first ischemic stroke in participants with both folate and B12 below the median (2.3% in enalapril-folic acid group vs 3.6% in enalapril-only group; HR, 0.62; 95% CI, 0.46-0.86), particularly in MTHFR 677 CC carriers (1.6% vs 4.9%; HR, 0.24; 95% CI, 0.11-0.55). However, TT homozygotes responded better with both folate and B12 levels above the median (HR, 0.28; 95% CI, 0.10-0.75).ConclusionsThe risk of first ischemic stroke was significantly higher in hypertensive patients with low levels of both folate and B12. Effect of folic acid treatment was greatest in patients with low folate and B12 with the CC genotype, and with high folate and B12 with the TT genotype.
AB - ObjectiveWe evaluated the interaction of serum folate and vitamin B12 with methylenetetrahydrofolate reductase (MTHFR) C677T genotypes on the risk of first ischemic stroke and on the efficacy of folic acid treatment in prevention of first ischemic stroke.MethodsA total of 20,702 hypertensive adults were randomized to a double-blind treatment of daily enalapril 10 mg and folic acid 0.8 mg or enalapril 10 mg alone. Participants were followed up every 3 months.ResultsMedian values of folate and B12 concentrations at baseline were 8.1 ng/mL and 280.2 pmol/L, respectively. Over a median of 4.5 years, among those not receiving folic acid, participants with baseline serum B12 or serum folate above the median had a significantly lower risk of first ischemic stroke (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.57-0.96), especially in those with MTHFR 677 CC genotype (wild-type) (HR, 0.49; 95% CI, 0.31-0.78). Folic acid treatment significantly reduced the risk of first ischemic stroke in participants with both folate and B12 below the median (2.3% in enalapril-folic acid group vs 3.6% in enalapril-only group; HR, 0.62; 95% CI, 0.46-0.86), particularly in MTHFR 677 CC carriers (1.6% vs 4.9%; HR, 0.24; 95% CI, 0.11-0.55). However, TT homozygotes responded better with both folate and B12 levels above the median (HR, 0.28; 95% CI, 0.10-0.75).ConclusionsThe risk of first ischemic stroke was significantly higher in hypertensive patients with low levels of both folate and B12. Effect of folic acid treatment was greatest in patients with low folate and B12 with the CC genotype, and with high folate and B12 with the TT genotype.
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U2 - 10.1212/WNL.0000000000008932
DO - 10.1212/WNL.0000000000008932
M3 - Article
C2 - 31932513
AN - SCOPUS:85079711316
SN - 0028-3878
VL - 94
SP - e1126-e1136
JO - Neurology
JF - Neurology
IS - 11
ER -