Because mice appear to show mostly single gene inheritance for NTDs and humans show multifactorial inheritance, mice sometimes have been characterized as a simpler model for the identification and study of NTD genes.But are they a simple model?
Possible interaction of genotypes at cystathionine beta-synthase and methylenetetrahydrofolate reductase (MTHFR) in neural tube defects. NTD Collaborative Group.
Genetic correlation of human neural tube defects (NTDs) with NTD genes identified in mouse may unravel predisposing complex traits for assessment of individual risk and treatment in clinical settings.
The thermolabile variant of methylenetetrahydrofolate reductase (MTHFR) is not a major risk factor for neural tube defect in American Caucasians. The NTD Collaborative Group.
Omphalocele cases were significantly more likely to carry the T allele of MTHFR 677C-->T, a known risk factor for NTDs (odds ratio 3.50, 95% confidence interval 1.07-11.47, P=0.035).
Low folate intake as well as alterations in folate metabolism as a result of polymorphisms in the enzyme methylenetetrahydrofolate reductase (MTHFR) have been associated with an increased incidence of neural tube defects, vascular disease, and some cancers.
When broken down into the various 677 ct MTHFR and 2756ag MetSyn genotypes, carriage of the 677ct MTHFR allele appears to affect formyl-H(4)PteGlu metabolism in non-NTD mothers.
Several experimental studies in mice and human epidemiological and genetics studies have suggested that folate receptor abnormalities are involved in a portion of human NTDs, although the solo defect of FOLR1 did not cause NTD.
In our study, an increased risk of NTD was observed for 1958G>A of MTHFD1 (AA vs. GG: OR=2.63, 95% CI=2.61-5.70; AA vs. GG+GA: OR=2.10, 95% CI=1.07-4.14; A vs. G: OR=1.62, 95% CI=1.11-2.36).
Our meta-analysis strongly suggested a significant association of the variant MTHFRC677T and a suggestive association of RFC-1 A80G with increased risk of NTDs.
This study, though preliminary, provides the first genetic association between molecular variations of the FRalpha gene and NTDs and suggests that this gene can act as a risk factor for human NTD.
Gene variants in the folate metabolic pathway (e.g., MTHFR rs1801133 (677 C > T) and MTHFD1rs2236225 (rs2236225" genes_norm="1788;4522">R653Q)) have been found to increase NTD risk.
This study aims to evaluate the association between genetic defects in folate metabolism pathway genes, mainly: Folate hydrolase 1 (FOLH1), Dihydrofolate reductase (DHFR) and Methylenetetrahydrofolate reductase (MTHFR) and neural tube defects from eastern India.
Moreover, some authors demonstrated association of the C-->T mutation (C677T), converting an alanine to a valine residue in 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, with other congenital anomalies such as neural tube defects (NTDs).
We conclude that genetic variation in the MTHFD1 gene is associated with an increase in the genetically determined risk that a woman will bear a child with NTD and that the gene may be associated with decreased embryo survival.
The aim of this study was to evaluate whether the cytosine-to-thymine mutation at base 677 of the methylenetetrahydrofolate reductase gene (MTHFRC677T), which has been associated with neural tube defects and congenital oral cleft, is also associated with tetralogy of Fallot (TF), a congenital heart disease.
A common mutation, C677T, in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene leads to altered homocysteine metabolism, and has been associated with the occurrence of neural tube defects (NTD).