Plasma total homocysteine levels and the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene: a study in an Italian population with dementia

Abstract Background: Plasma total homocysteine (tHcy) is a risk factor for cardiovascular disease. tHcy concentrations are partly determined by folate, cobalamin, and vitamin B6 status, and methylenetetrahydrofolate reductase (MTHFR) and other flavoenzymes are important for the biotransformation of these vitamins. This motivates the investigation of the possible relationship between riboflavin status and tHcy. Methods: The study had a cross-sectional design and included 423 healthy blood donors, ages 19–69 years. We determined plasma tHcy, serum folate, serum cobalamin, serum creatinine, and MTHFR C677T genotype. In addition, we measured riboflavin and its two coenzyme forms, flavin mononucleotide and flavin adenine dinucleotide, in EDTA plasma by capillary electrophoresis and laser-induced fluorescence detection. Results: Riboflavin determined tHcy independently in a multiple linear regression model with adjustment for sex, age, folate, cobalamin, creatinine, and MTHFR genotype (P = 0.008). tHcy was 1.4 μmol/L higher in the lowest compared with the highest riboflavin quartile. The riboflavin-tHcy relationship was modified by genotype (P = 0.004) and was essentially confined to subjects with the C677T transition of the MTHFR gene. Conclusions: Plasma riboflavin is an independent determinant of plasma tHcy. Studies on deficient populations are needed to evaluate the utility of riboflavin supplementation in hyperhomocysteinemia.

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Effect of Mthfr genotype on diet-induced hyperhomocysteinemia and vascular function in mice

Blood ◽

10.1182/blood-2003-09-3078 ◽

2004 ◽

Vol 103 (7) ◽

pp. 2624-2629 ◽

Cited By ~ 81

Author(s):

Angela M. Devlin ◽

Erland Arning ◽

Teodoro Bottiglieri ◽

Frank M. Faraci ◽

Rima Rozen ◽

...

Keyword(s):

Vascular Function ◽

Methylenetetrahydrofolate Reductase ◽

Control Diet ◽

Mthfr Gene ◽

Cerebral Microvessels ◽

Mthfr Genotype ◽

Methylation Capacity ◽

Cerebral Arterioles ◽

Total Homocysteine ◽

Plasma Total Homocysteine

Abstract Deficiency of methylenetetrahydrofolate reductase (MTHFR) predisposes to hyperhomocysteinemia and vascular disease. We tested the hypothesis that heterozygous disruption of the Mthfr gene sensitizes mice to diet-induced hyperhomocysteinemia and endothelial dysfunction. Mthfr+/- and Mthfr+/+ mice were fed 1 of 4 diets: control, high methionine (HM), low folate (LF), or high methionine/low folate (HM/LF). Plasma total homocysteine (tHcy) was higher with the LF and HM/LF diets than the control (P < .01) or HM (P < .05) diets, and Mthfr+/- mice had higher tHcy than Mthfr+/+ mice (P < .05). With the control diet, the S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH) ratio was lower in the liver and brain of Mthfr+/- mice than Mthfr+/+ mice (P < .05). SAM/SAH ratios decreased further in Mthfr+/+ or Mthfr+/- mice fed LF or LF/HM diets (P < .05). In cerebral arterioles, endothelium-dependent dilation to 1 or 10 μM acetylcholine was markedly and selectively impaired with the HM/LF diet compared with the control diet for both Mthfr+/+ (maximum dilation 5% ± 2% versus 21% ± 4%; P < .01) and Mthfr+/- (6% ± 2% versus 21% ± 3%; P < .01) mice. These findings demonstrate that the Mthfr+/- genotype sensitizes mice to diet-induced hyperhomocysteinemia and that hyperhomocysteinemia alters tissue methylation capacity and impairs endothelial function in cerebral microvessels.

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The effect of 677C → T and 1298A → C mutations on plasma homocysteine and 5,10-methylenetetrahydrofolate reductase activity in healthy subjects

British Journal Of Nutrition ◽

10.1017/s0007114500000751 ◽

2000 ◽

Vol 83 (6) ◽

pp. 593-596 ◽

Cited By ~ 100

Author(s):

A. Chango ◽

F. Boisson ◽

F. Barbé ◽

D. Quilliot ◽

...

Keyword(s):

Methylenetetrahydrofolate Reductase ◽

Specific Activity ◽

Reductase Activity ◽

Mthfr Gene ◽

High Serum ◽

Serum Folate ◽

Vitamin B ◽

Serum Folate Level ◽

Total Homocysteine ◽

Plasma Total Homocysteine

We have studied the effect of common mutations (677C → T and 1298A → C) of the methylenetetrahydrofolate reductase (MTHFR) gene in sixty-six healthy French subjects, aged 27–47 years. Serum folate, vitamin B12, and plasma total homocysteine were measured as well as the specific activity of MTHFR in lymphocytes. The frequency of subjects homozygous for the 677TT genotype was 18 %, and that of those homozygous for the 1298CC genotype was 12·5 %. The frequency of individuals heterozygous for both mutations was 23·5 %. The 1298A → C mutation was associated with decreased MTHFR specific activity in subjects with both 677CC and 677CT genotypes. This activity was 60 % for the 677CC/1298AC genotype and 52 % for the 677CC/1298CC genotype when compared with the MTHFR specific activity of the 677CC/1298AA genotype. Heterozygotes for both mutations (677CT/1298AC genotype) had 36 % of the reference specific activity. Although homocysteine levels in 677TT and 1298CC genotype subjects were higher than for other genotypes, no significant differences were observed among different genotypes. This may be due to high serum folate level in our samples, and suggests that folate therapy may be useful to prevent hyperhomocysteinaemia in homozygous mutant subjects.

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Elevated plasma total homocysteine and C677T mutation of the methylenetetrahydrofolate reductase gene in patients with spina bifida

QJM ◽

10.1093/qjmed/90.9.593 ◽

1997 ◽

Vol 90 (9) ◽

pp. 593-596 ◽

Cited By ~ 18

Author(s):

A. L. Bjorke-Monsen ◽

P. M. Ueland ◽

J. Schneede ◽

S. E. Vollset ◽

H. Refsum

Keyword(s):

Spina Bifida ◽

Methylenetetrahydrofolate Reductase ◽

Elevated Plasma ◽

Reductase Gene ◽

C677t Mutation ◽

Total Homocysteine ◽

Plasma Total Homocysteine ◽

Methylenetetrahydrofolate Reductase Gene

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Methylenetetrahydrofolate reductase polymorphisms as risk factors for retinal venous occlusive disease: A literature review

European Journal of Ophthalmology ◽

10.1177/11206721211000647 ◽

2021 ◽

pp. 112067212110006

Author(s):

Manuel Marques ◽

Francisco Alves ◽

Miguel Leitão ◽

Catarina Rodrigues ◽

Joana Tavares Ferreira

Keyword(s):

Risk Factors ◽

Literature Review ◽

Methylenetetrahydrofolate Reductase ◽

Mthfr C677t ◽

Mthfr Gene ◽

Mthfr Polymorphisms ◽

Vein Occlusion ◽

C677t Mutation ◽

Retinal Vascular Disease

The role of polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene in retinal vein occlusion (RVO) is a theme of discussion since the first reports of RVO in patients with MTHFR C677T mutation and without classic acquired risk factors for retinal vascular disease. The association between MTHFR polymorphisms and RVO has been studied over the last 20 years producing conflicting results. This review aims to summarize the literature concerning the role MTHFR polymorphisms as risk factors for RVO.

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Ethnic Differences in the Frequency of the C677T Mutation in the Methylenetetrahydrofolate Reductase (MTHFR) Gene in Healthy Israeli Populations

Genetic Testing ◽

10.1089/10906570050501560 ◽

2000 ◽

Vol 4 (3) ◽

pp. 309-311 ◽

Cited By ~ 15

Author(s):

Rivka Dresner Pollak ◽

Yechiel Friedlander ◽

Arthur Pollak ◽

Maria Idelson ◽

Idit Bejarano-Achache ◽

...

Keyword(s):

Ethnic Differences ◽

Methylenetetrahydrofolate Reductase ◽

Mthfr Gene ◽

C677t Mutation

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Hyperhomocysteinemia and C677T Polymorphism of Methylenetetrahydrofolate Reductase Gene in Patients with Cardiovascular Disease

Pteridines ◽

10.1515/pteridines.2010.21.1.103 ◽

2010 ◽

Vol 21 (1) ◽

pp. 103-109

Author(s):

Zahira Houcher ◽

Bakhouche Houcher ◽

Abderezak Touabti ◽

Samia Begag ◽

Ayşenur Öztürk ◽

...

Keyword(s):

Cardiovascular Disease ◽

Methylenetetrahydrofolate Reductase ◽

Mthfr C677t ◽

C677t Polymorphism ◽

Old Patients ◽

Mthfr C677t Polymorphism ◽

Plasma Thcy ◽

C677t Mutation ◽

Total Homocysteine ◽

And Gender

Abstract The aim of the present study was to explore the influence of age and gender, on the association between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and plasma total homocysteine (tHcy) concentrations in patients with cardiovascular disease (CVD). Fasting tHcy and the MTHFR C677T mutation were evaluated in 98 patients with CVD, 46 were men and 52 women (aged 20-96 years). There was a significant elevation of plasma tHcy with age (<45 yr: 33.9 μmol/L vs. >75 yr: 43.6 μmol/L; p <0.01). The mean tHcy concentration increased significantly with age in men (<55 yr: 33.4 μmol/L vs. >55yr: 42.45 μmol/L; p 0.01). However, the plasma tHcy was not increased with older age in women. The frequency of the TT genotype was 19.6% in the younger patients group (>55 yr) compared with 4.7% in the older patients group (>55 yr; p <0.01). In conclusion, the data presented here are consistent with genetic factors that influence tHcy levels being more prominent in old patients (>55 yr). Then, the MTHFR mutation does not seem to be associated with either high tHcy or the occurrence of CVD.

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