Impact of the MTHFR C677T polymorphism on risk of neural tube defects: case-control study

  title={Impact of the MTHFR C677T polymorphism on risk of neural tube defects: case-control study},
  author={Peadar N. Kirke and James L. Mills and Anne M. Molloy and Lawrence C. Brody and Valerie Br{\'i}d O'Leary and Leslie E. Daly and Sharon Murray and Mary R. Conley and Philip D. Mayne and Owen P Smith and John M. Scott},
  journal={BMJ : British Medical Journal},
  pages={1535 - 1536}
Homozygosity for the T allele of the C677T polymorphism of the gene encoding the folate dependent enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) is a risk factor for neural tube defects.1 Both the homozygous (TT) and heterozygous (CT) genotypes are associated with lower tissue concentrations of folate, higher homocysteine concentrations, and lower enzyme activity than the wild type (CC) genotype; these effects are more marked in homozygotes. Low folate and raised homocysteine levels in… 
C677T mutation in methylenetetrahydrofolate reductase gene and neural tube defects: Should Japanese women undergo gene screening before pregnancy?
It is not necessary for Japanese women to undergo genetic screening C677T mutation of the MTHFR gene as a predictive marker for spina bifida prior to pregnancy, because the TT genotype is not a risk factor for having an affected infant.
Study of C677T Methylene Tetrahydrofolate Reductase Gene Polymorphism as a Risk Factor for Neural Tube Defects
There was no evidence of association between MTHFR C677T polymorphism and NTDs, but this study does not rule out the impact of MTHfr gene mutation on folate metabolism.
Variants in MTHFR gene and neural tube defects susceptibility in China
This study revealed that the SNPs of 677C > T and 1298A > C in MTHFR were associated with NTD-affected pregnancy, in which 677 c > T was a risk factor and in contrast 1298 a > C was protective factor against NTD.
Folate supplementation, MTHFR gene polymorphism and neural tube defects: a community based case control study in North India
There was no significant difference in the genotypic or allelic distribution of MTHFR C677T polymorphism, however, high frequency of CT genotype, as observed, among controls suggests heterozygous advantage probably due to supplementary folate.
Association between MTHFR C677T polymorphism and neural tube defect risks: A comprehensive evaluation in three groups of NTD patients, mothers, and fathers.
No association between any of the fathers' genotypes and NTDs is found, whereas a significant correlation between MTHFR C677T polymorphism and N TD risk was found in NTD patients and in their mother.
Effect on risk of anencephaly of gene–nutrient interactions between methylenetetrahydrofolate reductase C677T polymorphism and maternal folate, vitamin B12 and homocysteine profile
The data agree with the hypothesis of a gene–nutrient interaction between MTHFR 677C→T polymorphism and folate status and a protective effect on anencephaly risk only in mothers with 677TT genotype as serum folate levels increased.
Variants in maternal COMT and MTHFR genes and risk of neural tube defects in offspring
The interaction of COMT rs737865 and MTHFR C677T was associated with an increased risk of N TDs, especially anencephaly, in a Chinese population with a high prevalence of NTDs.
No evidence for association of MTHFR 677C>T and 1298A>C variants with placental DNA methylation
It is concluded that large-scale, genome-wide disruption in DNAm does not occur in placentas with the high-risk MTHFR 677TT or 1298CC genotypes and investigations into alternative mechanisms that may explain the link between MTH FR variants and pregnancy complications, or in populations at risk of folate deficiencies are warranted.
MTHFR C 677 T Polymorphism as a Risk Factor of Neural Tube Defects in Malay : A Case Control Study
Results show that MTHFR 677TT genotype was absent in both patient and control groups, and it was hypothesized that the maternal folic acid supplementation prevents NTDs by partially correcting reduced MTH FR activity associated with the variant form of the enzyme.
Polymorphisms of 5,10-Methylenetetrahydrofolate Reductase and Cystathionine β-Synthase Genes as a Risk Factor for Neural Tube Defects in Sétif, Algeria
The results with Algerian NTD mothers did not show a significant association for any group, suggesting that the thermolabile variant C677T in the MTHFR gene is not a risk factor for a mother to have NTD offspring; rather, folic acid supplementation or fortification should become mandatory for all women of reproductive age in Algeria.


The "thermolabile" variant of methylenetetrahydrofolate reductase and neural tube defects: An evaluation of genetic risk and the relative importance of the genotypes of the embryo and the mother.
A biological model of MTHFR-related NTD pathogenesis is favored, in which suboptimal maternal folate status imposes biochemical stress on the developing embryo, a stress it is ill-equipped to tolerate if it has a TT genotype.
5,10-Methylenetetrahydrofolate reductase gene variants and congenital anomalies: a HuGE review.
The risk for spina bifida associated with C677T homozygosity may depend on nutritional status or on the genotype of other folate-related genes (e.g., cystathionine-beta-synthase and methionine synthase reductase).
Comorbidity of 5,10-methylenetetrahydrofolate reductase and methionine synthase gene polymorphisms and risk for neural tube defects
Women with an NTD affected pregnancy do not usually have overt signs of folate deficiency, although decreased erythrocyte folate concentration, the index known to reflect whole body folate stores, has been reported, suggesting that folate metabolism may be altered in these women.
Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis
Whether the association of serum homocysteine concentration with ischaemic heart disease, deep vein thrombosis and pulmonary embolism, and stroke is causal and, if so, to quantify the effect of homocy Steine reduction in preventing them, there is strong evidence that the association between homocy steine and cardiovascular disease is causal.
Homocysteine and Cardiovascular Disease
After a thorough review of the available literature, it appears that hyperhomocysteinemia is an independent risk factor for CHD. Furthermore, folic acid has been shown to reduce homocysteine
Homocysteine and cardiovascular disease.
An elevated level of total homocysteine (tHcy) in blood, denoted hyperhomocysteinemia, is emerging as a prevalent and strong risk factor for atherosclerotic vascular disease in the coronary,
Stone assistant professor of nursing continued over BMJ 2004;328:1536–7
  • 2004