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MTHFR C677T and MTR A2756G polymorphisms and the homocysteine lowering efficacy of different doses of folic acid in hypertensive Chinese adults

Xianhui Qin1, Jianping Li2, Yimin Cui3, Zeyuan Liu4, Zhigang Zhao5, Junbo Ge6, Deming Guan7, Jian Hu8, Yanni Wang9, Fumin Zhang10, Xin Xu11, Xiaobin Wang12, Xiping Xu1* and Yong Huo2*

Author Affiliations

1 Institute of Biomedicine, Anhui Medical University, Hefei, China

2 Department of Cardiology and Heart Center, Peking University First Hospital, Beijing, China

3 Department of Pharmacy, Peking University First Hospital, Beijing, China

4 Department of Pharmacy, First Affiliated Hospital of Academy of Military Medical, Sciences of China, Beijing, China

5 Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

6 Department of Cardiology, Zhongshan Hospital Fudan University, Shanghai, China

7 Department of Cardiology, First Clinical Medical College of Harbin Medical University, Harbin, China

8 Department of Cardiology, First Affiliated Hospital of China Medical University, Shenyang, China

9 Department of Cardiology, First Affiliated Hospital of the School of Medicine, Xi'an Jiaotong University, Xi'an, China

10 Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China

11 Guangdong Institute of Nephrology, Southern Medical University, Guangzhou, China

12 Mary Ann and J. Milburn Smith Child Health Research Program, Children's Memorial Hospital and Children's Memorial Research Center, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, USA

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Nutrition Journal 2012, 11:2  doi:10.1186/1475-2891-11-2

Published: 10 January 2012



This study aimed to investigate if the homocysteine-lowering efficacy of two commonly used physiological doses (0.4 mg/d and 0.8 mg/d) of folic acid (FA) can be modified by individual methylenetetrahydrofolate reductase (MTHFR) C677T and/or methionine synthase (MTR) A2756G polymorphisms in hypertensive Chinese adults.


A total of 480 subjects with mild or moderate essential hypertension were randomly assigned to three treatment groups: 1) enalapril only (10 mg, control group); 2) enalapril-FA tablet [10:0.4 mg (10 mg enalapril combined with 0.4 mg of FA), low FA group]; and 3) enalapril-FA tablet (10:0.8 mg, high FA group), once daily for 8 weeks.


After 4 or 8 weeks of treatment, homocysteine concentrations were reduced across all genotypes and FA dosage groups, except in subjects with MTR 2756AG /GG genotype in the low FA group at week 4. However, compared to subjects with MTHFR 677CC genotype, homocysteine concentrations remained higher in subjects with CT or TT genotype in the low FA group (P < 0.05 for either of these genotypes) and TT genotype in the high FA group (P < 0.05). Furthermore, subjects with TT genotype showed a greater homocysteine-lowering response than did subjects with CC genotype in the high FA group (mean percent reduction of homocysteine at week 8: CC 10.8% vs. TT: 22.0%, P = 0.005), but not in the low FA group (CC 9.9% vs. TT 11.2%, P = 0.989).


This study demonstrated that MTHFR C677T polymorphism can not only affect homocysteine concentration at baseline and post-FA treatment, but also can modify therapeutic responses to various dosages of FA supplementation.

Folic acid supplementation; MTHFR C677T polymorphism; MTR A2756G polymorphism; Homocysteine-lowering efficacy