FCCC LOGO Faculty Publications
Huang X , Qin X , Yang W , Liu L , Jiang C , Zhang X , Jiang S , Bao H , Su H , Li P , He M , Song Y , Zhao M , Yin D , Wang Y , Zhang Y , Li J , Yang R , Wu Y , Hong K , Wu Q , Chen Y , Sun N , Li X , Tang G , Wang B , Cai Y , Hou FF , Huo Y , Wang H , Wang X , Cheng X
MTHFR Gene and Serum Folate Interaction on Serum Homocysteine Lowering: Prospect for Precision Folic Acid Treatment
Arterioscler Thromb Vasc Biol. 2018 Mar;38(3) :679-685
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Abstract
OBJECTIVE: This post hoc analysis of the CSPPT (China Stroke Primary Prevention Trial) assessed the individual variation in total homocysteine (tHcy)-lowering response after an average 4.5 years of 0.8 mg daily folic acid therapy in Chinese hypertensive adults and evaluated effect modification by methylenetetrahydrofolate reductase (MTHFR) C677T genotypes and serum folate levels. APPROACH AND RESULTS: This analysis included 16 413 participants from the CSPPT, who were randomly assigned to 2 double-blind treatment groups: either 10-mg enalapril+0.8-mg folic acid or 10-mg enalapril, daily and had individual measurements of serum folate and tHcy levels at baseline and exit visits and MTHFR C677T genotypes. Mean baseline tHcy levels were comparable between the 2 treatment groups (14.5+/-8.5 versus 14.4+/-8.1 mumol/L; P=0.561). After 4.5 years of treatment, mean tHcy levels were reduced to 12.7+/-6.1 mumol/L in the enalapril+folic acid group, but almost stayed the same in the enalapril group (14.4+/-7.9 mumol/L, group difference: 1.61 mumol/L; 11% reduction). More importantly, tHcy lowering varied by MTHFR genotypes and serum folate levels. Compared with CC and CT genotypes, participants with the TT genotype had a more prominent L-shaped curve between tHcy and serum folate levels and required higher folate levels (at least 15 ng/mL) to eliminate the differences in tHcy by genotypes. CONCLUSIONS: Compared with CC or CT, tHcy in the TT group manifested a heightened L-shaped curve from low to high folate levels, but this difference in tHcy by genotype was eliminated when plasma folate levels reach approximately 15 ng/mL or higher. Our data raised the prospect to tailor folic acid therapy according to individual MTHFR C677T genotype and folate status. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794885.
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1524-4636 Huang, Xiao Qin, Xianhui Yang, Wenbin Liu, Lishun Jiang, Chongfei Zhang, Xianglin Jiang, Shanqun Bao, Huihui Su, Hai Li, Ping He, Mingli Song, Yun Zhao, Min Yin, Delu Wang, Yu Zhang, Yan Li, Jianping Yang, Renqang Wu, Yanqing Hong, Kui Wu, Qinhua Chen, Yundai Sun, Ningling Li, Xiaoying Tang, Genfu Wang, Binyan Cai, Yefeng Hou, Fan Fan Huo, Yong Wang, Hong Wang, Xiaobin Cheng, Xiaoshu Journal Article United States Arterioscler Thromb Vasc Biol. 2018 Jan 25. pii: ATVBAHA.117.310211. doi: 10.1161/ATVBAHA.117.310211.