机构：[1]Department of Cardiology, The Second Affiliated Hospital of Nanchang University, China[2]National Clinical Research Study Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China[3]Institute of Biomedicine, Anhui Medical University, Hefei, China[4]China Agricultural University, Beijing[5]School of Life Sciences, Anhui University, Hefei, China[6]Department of Neurology, First People’s Hospital, Lianyungang, China[7]Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China广东省中医院[8]Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, China[9]Department of Cardiology, Peking University First Hospital, Beijing, China[10]Department of Cardiology, General Hospital of PLA, Beijing, China[11]Department of Cardiology, Peking University People’s Hospital, Beijing, China[12]Department of Geriatric Cardiology, the General Hospital of the People’s Liberation Army, Beijing, China[13]Centers for Metabolic Disease Research, Temple University School of Medicine, Philadelphia, PA[14]Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD
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 16413 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 (14.58.5 versus 14.48.1 mol/L; P=0.561). After 4.5 years of treatment, mean tHcy levels were reduced to 12.7 +/- 6.1 mol/L in the enalapril+folic acid group, but almost stayed the same in the enalapril group (14.4 +/- 7.9 mol/L, group difference: 1.61 mol/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 approximate to 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.
基金：
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).
第一作者机构：[1]Department of Cardiology, The Second Affiliated Hospital of Nanchang University, China
通讯作者：
通讯机构：[1]Department of Cardiology, The Second Affiliated Hospital of Nanchang University, China[13]Centers for Metabolic Disease Research, Temple University School of Medicine, Philadelphia, PA[14]Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD[*1]Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, 615 N Wolfe St, E4132, Baltimore, MD 21205,[*2]Department of Cardiology, Second Affiliated Hospital of Nanchang University, Jiangxi, China[*3]Centers for Metabolic Disease Research, Temple University School of Medicine, Philadelphia, PA
推荐引用方式(GB/T 7714)：
Huang Xiao,Qin Xianhui,Yang Wenbin,et al.MTHFR Gene and Serum Folate Interaction on Serum Homocysteine Lowering: Prospect for Precision Folic Acid Treatment[J].ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY.2018,38(3):679-685.doi:10.1161/ATVBAHA.117.310211.
APA：
Huang, Xiao,Qin, Xianhui,Yang, Wenbin,Liu, Lishun,Jiang, Chongfei...&Cheng, Xiaoshu.(2018).MTHFR Gene and Serum Folate Interaction on Serum Homocysteine Lowering: Prospect for Precision Folic Acid Treatment.ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY,38,(3)
MLA：
Huang, Xiao,et al."MTHFR Gene and Serum Folate Interaction on Serum Homocysteine Lowering: Prospect for Precision Folic Acid Treatment".ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY 38..3(2018):679-685
医学