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This study aimed to investigate if the homocysteine-lowering efficacy of two commonly used physiological doses (0.4mg/d and 0.8mg/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 (10mg, control group); 2) enalapril-FA tablet [10:0.4mg (10mg enalapril combined with 0.4mg of FA), low FA group]; and 3) enalapril-FA tablet (10:0.8mg, high FA group), once daily for 8 weeks. ResultsAfter 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.
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.
This article was published in the following journal.
Name: Nutrition journal
Methylenetetrahydrofolate reductase (MTHFR) is key enzyme of folate/homocysteine pathway. Case control association studies on MTHFR C677T polymorphism and Alzheimer's disease (AD) have been repeatedly...
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The C677T polymorphism in the MTHFR gene is related to several significant biochemical changes, as dyslipidemia, changes in serum levels of homocysteine, folic acid, vitamin B12 and some o...
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Randomized double-blind placebo controlled study of reduced B vitamins in patients with major depression who were positive for one or both of the common MTHFR polymorphisms. Homocysteine l...
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The development of diabetic nephropathy has been linked to several genetic polymorphisms, including those related with homocysteine metabolism such as the methylenetetrahydrofolate reducta...
An enzyme that catalyzes the demethylation of L-homocysteine to L-METHIONINE.
An enzyme that catalyzes the formation of methionine by transfer of a methyl group from 5-methyltetrahydrofolate to homocysteine. It requires a cobamide coenzyme. The enzyme can act on mono- or triglutamate derivatives. EC 126.96.36.199.
A ZINC metalloenzyme that catalyzes the transfer of a methyl group from BETAINE to HOMOCYSTEINE to produce dimethylglycine and METHIONINE, respectively. This enzyme is a member of a family of ZINC-dependent METHYLTRANSFERASES that use THIOLS or selenols as methyl acceptors.
Condition in which the plasma levels of homocysteine and related metabolites are elevated (>13.9 μmol/l). Hyperhomocysteinemia can be familial or acquired. Development of the acquired hyperhomocysteinemia is mostly associated with vitamins B and/or folate deficiency (e.g., PERNICIOUS ANEMIA, vitamin malabsorption). Familial hyperhomocysteinemia often results in a more severe elevation of total homocysteine and excretion into the urine, resulting in HOMOCYSTINURIA. Hyperhomocysteinemia is a risk factor for cardiovascular and neurodegenerative diseases, osteoporotic fractures and complications during pregnancy.
The relative equivalency in the efficacy of different modes of treatment of a disease, most often used to compare the efficacy of different pharmaceuticals to treat a given disease.