Biological and clinical implications of the MTHFR C677T polymorphism

Ueland, Per Magne; Hustad, Steinar; Schneede, Jörn; Refsum, Helga; Vollset, Stein Emil

doi:10.1016/s0165-6147(00)01675-8

Cited by 469 publications

(373 citation statements)

References 53 publications

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“…Serum homocysteine was negatively correlated with serum folate in our study subjects of all the three MTHFR genotypes, and the correlation between the two serum levels was strongest as had been previously reported by Ueland et al (2001) and Guttormsen et al (1996), who had observed a steeper negative slope in plots of serum folate vs serum homocysteine concentration in T/T individuals compared to those in the C/T or C/C subjects. The results of our study suggest that pregnant women with a combination of decreased serum folate concentrations and the T/T genotype of the MTHFR gene could be at an increased risk of developing hyperhomocysteinemia, confirming the previous findings by Powers et al (1999).…”

Section: Discussionsupporting

confidence: 88%

“…An earlier animal study showed a significant association between vitamin B 2 and MTHFR that the enzyme activity and the relative amounts of 5-methyl THF were reduced in the liver of riboflavin-deficient rats (Bates & Fuller, 1986). Hustad et al (2000), McNulty et al (2002), and Jacques et al (2002) demonstrated that plasma vitamin B 2 was an independent determinant of plasma homocysteine, and this inverse dose-response relation was essentially confined to subjects with the C/T or T/T genotype of the MTHFR C677T polymorphism where the requirement of FAD for maximal catalytic activity might be increased (Hustad et al, 2000;Ueland et al, 2001). Several investigators have suggested that vitamin B 6 deficiency may lead to hyperhomocysteinemia, which is an established risk factor for adverse pregnancy outcome (van den Berg et al, 1994;Leeda et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

“…Homocysteine is influenced by the nutritional status of B vitamins (vitamin B 2 , vitamin B 6, folate, and vitamin B 12 ), whose metabolic steps are inter-related with each other (Perry, 1999;Ueland et al, 2001) and nutritional adequacy of these vitamins is essential to maintain the plasma homocysteine levels within a normal homeostatic range. The conversion step of tetrahydrofolate (THF) to 5,10-methylene THF is coupled with a PLP-dependent reaction and that of 5,10-methylene THF to 5-methyl THF, a FAD-dependent reaction, and the regeneration of THF from 5-methyl THF is a vitamin B 12 -dependent reaction.…”

Section: Introductionmentioning

confidence: 99%

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Effects of the interaction between the C677T 5,10-methylenetetrahydrofolate reductase polymorphism and serum B vitamins on homocysteine levels in pregnant women

Kim

Chang

2003

Eur J Clin Nutr

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Objective: The purpose of this study was to investigate the effect of the interaction between the C677T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) genotypes and serum levels of B vitamins on serum homocysteine levels in pregnant women. Design: A cross-sectional study. Setting: Ewha Womans University Hospital, Seoul, Korea. Subjects: A total of 177 normal pregnant women, 24.671.1 weeks of gestation, in a 6-month period during [2001][2002]. Interventions: Serum vitamin B 2 , vitamin B 6 , and homocysteine analyses were conducted using high-performance liquid chromatography methods. Serum folate and vitamin B 12 concentrations were determined using a radioimmunoassay kit. MTHFR gene mutation was investigated by the polymerase chain reaction of a genomic DNA fragment. Results: Serum homocysteine was higher in women with the T/T genotype than those with the C/T or C/C genotype of the MTHFR gene (Po0.05). Serum homocysteine was negatively correlated with serum folate in all MTHFR genotypes (Po0.001), and the correlation between the two serum levels was the strongest in the T/T genotype. Serum homocysteine was higher in the subjects with the T/T MTHFR genotype only when the serum folate was below the median level. Explanatory power of B vitamin status as predictors of serum homocysteine levels was more pronounced in the T/T genotypes (68.5%) compared with the C/T (37.9%) or C/C genotypes (20.6%). Conclusions: Serum homocysteine levels in pregnant women varied significantly with MTHFR genotype and the serum B vitamin status. Higher serum folate, vitamin B 2 , and vitamin B 12 concentrations may lessen the MTHFR genotypic effect on serum homocysteine levels.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of the interaction between the C677T 5,10-methylenetetrahydrofolate reductase polymorphism and serum B vitamins on homocysteine levels in pregnant women

Kim

Chang

2003

Eur J Clin Nutr

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“…Identified in 1995, 31 the MTHFR C677T polymorphism, encoding a One-carbon folate pathway genetics DF Carr et al valine to alanine amino-acid substitution at residue 222, has a long established and marked effect on folate and homocysteine levels. 32 Phenotypically, this variant protein has reduced catalytic activity and thermolability, and is thus associated with elevated homocysteine levels under conditions of impaired folate status. A vast amount of research investigating MTHR C677T and A1298C (rs1801131) as disease risk factors has been conducted.…”

Section: Mthfrmentioning

confidence: 99%

Investigation of inter-individual variability of the one-carbon folate pathway: a bioinformatic and genetic review

2009

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“…Ainda, alguns autores têm voltado sua atenção ao estado vitamínico 7,8 e polimorfismos genéticos relacionados à HHcy 9 . Recentemente, estudos têm buscado entender o balanço da demanda de metilação e os efeitos da modulação de tal balanço sobre o metabolismo da homocisteína 4,10,11 .…”

Section: -Introduçãounclassified

Suplementação De Creatina, Homocisteína E Estresse Oxidativo

Deminice¹,

Vilhena²,

Portari³

et al. 2007

Medicina (Ribeirão Preto)

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Deminice R, Vilhena R, Portari GV, Jordão AA. Suplementação de creatina, homocisteína e estresse oxidativo.Medicina (Ribeirão Preto) 2007;40 (3): 368-77, jul./set. RESUMO:A creatina é uma substância popular entre atletas devido a sua possível propriedade ergogênica. Tal popularidade incentivou autores a estudar e explorar o possível potencial terapêutico desta substância. A síntese de creatina é responsável pela maioria das transferências de grupos metila no metabolismo hepático normal. Como a homocisteína é um aminoácido formado exclusivamente a partir da desmetilação da metionina, acredita-se que a creatina e homocisteína estejam metabolicamente conectadas. Estudos têm mostrado que a hiperhomocisteinemia está diretamente ligada à formação de espécies reativas de oxigênio pela autooxidação da homocisteína e/ou da cisteína e que tal auto-oxidação pode provocar danos celulares. O objetivo desta revisão é discutir aspectos da suplementação com creatina relacionados aos níveis de homocisteína e o estresse oxidativo.Descritores: Creatina. Suplementação Alimentar. Homocisteína. Estresse Oxidativo. 368Medicina, Ribeirão Preto, 2007; 40 (3): 368-77, jul./set. REVISÃO 1-INTRODUÇÃODevido aos seus possíveis efeitos no desempenho físico, a creatina (Cr) tornou-se um suplemento nutricional popular entre atletas principalmente a partir da década de 90. Recentemente, a creatina tem recebido considerável atenção na área médica. Alguns estudos têm mostrado efeitos benéficos da suplementação desta substância em pacientes ou modelos experimentais de diversas doenças como atrofia muscular, doenças cardiovasculares e neurodegenerativas 1,2,3 . Atualmente, alguma atenção tem sido dada para interação do metabolismo da homocisteína (Hcy) e da creatina e seu possível papel antioxidante 4,5 .Historicamente, autores que estudam a homocisteína, têm buscado entender as conseqüências de erros inatos sobre as enzimas que participam no metabolismo desse aminoácido e que resultam em hiperhomocisteinemia (HHcy) 6 . Ainda, alguns autores têm voltado sua atenção ao estado vitamínico 7,8 e polimorfismos genéticos relacionados à HHcy 9 . Recentemente, estudos têm buscado entender o balanço da demanda de metilação e os efeitos da modulação de tal balanço sobre o metabolismo da homocisteína 4,10,11 . Contudo, o objetivo desta revisão é discutir os efeitos da suplementação com creatina sobre os níveis de homocisteína, além do seu possível papel protetor contra a formação de espécies reativas de oxigênio, das interações e inter-relações da ingestão com a produção endógena de creatina.

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Biological and clinical implications of the MTHFR C677T polymorphism

Cited by 469 publications

References 53 publications

Effects of the interaction between the C677T 5,10-methylenetetrahydrofolate reductase polymorphism and serum B vitamins on homocysteine levels in pregnant women

Effects of the interaction between the C677T 5,10-methylenetetrahydrofolate reductase polymorphism and serum B vitamins on homocysteine levels in pregnant women

Investigation of inter-individual variability of the one-carbon folate pathway: a bioinformatic and genetic review

Suplementação De Creatina, Homocisteína E Estresse Oxidativo

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