TY - JOUR
T1 - MTHFR gene and serum folate interaction on serum homocysteine lowering prospect for precision folic acid treatment
AU - Huang, Xiao
AU - Qin, Xianhui
AU - Yang, Wenbin
AU - Liu, Lishun
AU - Jiang, Chongfei
AU - Zhang, Xianglin
AU - Jiang, Shanqun
AU - Bao, Huihui
AU - Su, Hai
AU - Li, Ping
AU - He, Mingli
AU - Song, Yun
AU - Zhao, Min
AU - Yin, Delu
AU - Wang, Yu
AU - Zhang, Yan
AU - Li, Jianping
AU - Yang, Renqang
AU - Wu, Yanqing
AU - Hong, Kui
AU - Wu, Qinhua
AU - Chen, Yundai
AU - Sun, Ningling
AU - Li, Xiaoying
AU - Tang, Genfu
AU - Wang, Binyan
AU - Cai, Yefeng
AU - Hou, Fan Fan
AU - Huo, Yong
AU - Wang, Hong
AU - Wang, Xiaobin
AU - Cheng, Xiaoshu
N1 - Funding Information:
All authors have completed the International Committee of Medical Journal Editors uniform disclosure form and have declared the following: X. Huang reports grants from the National Natural Science Foundation of China and Major Projects of the Science and Technology Department, Jiangxi, China. X. Cheng reports grant of Major Projects of the Science and Technology Department, Jiangxi, China. X. Qin reports grants from the National Science Foundation and consulting fees from AUSA Research Institute, Shenzhen; F.F. Hou reports grants from the Major State Basic Research Development Program of China, Ministry of Science and Technology of the People’s Republic of China, and the State Key Laboratory for Organ Failure Research, Guangzhou, China; B. Wang reports grants from the National Science Foundation, Department of Science and Innovation, and the Shenzhen Municipal Government and consulting fees from AUSA Research Institute, Shenzhen; Y. Huo reports grants from the National Major Scientific and Technological Special Project. The other authors report no conflicts.
Funding Information:
This work was supported in part by the National Natural Science Foundation of China grant (81500233), major projects of the Science and Technology Department, Jiangxi, China (20151BDH80038, 20171BAB205008, 20161BAB215239, and 20161BBH80073), and the National Institutes of Health grants (HL67033, HL77288, HL82774, HL-110764, HL130233, HL131460, DK104114, and DK113775 (H. Wang).
Publisher Copyright:
© 2018 American Heart Association, Inc.
PY - 2018
Y1 - 2018
N2 - 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 μmol/L; P=0.561). After 4.5 years of treatment, mean tHcy levels were reduced to 12.7±6.1 μmol/L in the enalapril+folic acid group, but almost stayed the same in the enalapril group (14.4±7.9 μmol/L, group difference: 1.61 μmol/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 15 ng/mL or higher. Our data raised the prospect to tailor folic acid therapy according to individual MTHFR C677T genotype and folate status.
AB - 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 μmol/L; P=0.561). After 4.5 years of treatment, mean tHcy levels were reduced to 12.7±6.1 μmol/L in the enalapril+folic acid group, but almost stayed the same in the enalapril group (14.4±7.9 μmol/L, group difference: 1.61 μmol/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 15 ng/mL or higher. Our data raised the prospect to tailor folic acid therapy according to individual MTHFR C677T genotype and folate status.
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U2 - 10.1161/ATVBAHA.117.310211
DO - 10.1161/ATVBAHA.117.310211
M3 - Article
C2 - 29371246
AN - SCOPUS:85047953107
SN - 1079-5642
VL - 38
SP - 679
EP - 685
JO - Arteriosclerosis, thrombosis, and vascular biology
JF - Arteriosclerosis, thrombosis, and vascular biology
IS - 3
ER -