MTHFR Gene and Serum Folate Interaction on Serum Homocysteine Lowering: Prospect for Precision Folic Acid Treatment.
Arterioscler Thromb Vasc Biol
; 38(3): 679-685, 2018 03.
Article
en En
| MEDLINE
| ID: mdl-29371246
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 ANDRESULTS:
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. CLINICAL TRIAL REGISTRATION URL http//www.clinicaltrials.gov. Unique identifier NCT00794885.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Complejo Vitamínico B
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Hiperhomocisteinemia
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Metilenotetrahidrofolato Reductasa (NADPH2)
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Ácido Fólico
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Homocisteína
Tipo de estudio:
Clinical_trials
/
Diagnostic_studies
/
Prognostic_studies
Límite:
Aged
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Female
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Humans
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Male
/
Middle aged
País/Región como asunto:
Asia
Idioma:
En
Revista:
Arterioscler Thromb Vasc Biol
Asunto de la revista:
ANGIOLOGIA
Año:
2018
Tipo del documento:
Article