Analysis of MTR and MTRR Polymorphisms for Neural Tube Defects Risk Association

Wang, Yongxin; Liu, Yuan; Ji, Wenyu; Hu, Qin; Wu, Hao; Xu, Danshu; Turtuohut, Tukebai; Wang, Zengliang

doi:10.1097/md.0000000000001367

Cited by 17 publications

(10 citation statements)

References 34 publications

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“…MTR is an enzyme that catalyzes the remethylation of Hcy to Met and is dependent on the provision of methyl groups from 5-MTHF (Figure 1). The mutation of MTR is associated with the increased risk of NTDs [6,19,29,30]. Solute carrier family 19 member 1 ( SCF19M1 ) can transport folate into cells.…”

Section: B-vitamins One-carbon Metabolism and Ntdsmentioning

confidence: 99%

Nutrition, One-Carbon Metabolism and Neural Tube Defects: A Review

Wahlqvist

2016

Nutrients

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Neural tube defects (NTDs) are a group of severe congenital malformations, induced by the combined effects of genes and the environment. The most valuable finding so far has been the protective effect of folic acid supplementation against NTDs. However, many women do not take folic acid supplements until they are pregnant, which is too late to prevent NTDs effectively. Long-term intake of folic acid–fortified food is a good choice to solve this problem, and mandatory folic acid fortification should be further promoted, especially in Europe, Asia and Africa. Vitamin B2, vitamin B-6, vitamin B-12, choline, betaine and n-3 polyunsaturated fatty acids (PUFAs) can also reduce the NTD risk by interacting with the one-carbon metabolism pathway. This suggest that multivitamin B combined with choline, betaine and n-3 PUFAs supplementation may have a better protective effect against NTDs than folic acid alone. Genetic polymorphisms involved in one-carbon metabolism are associated with NTD risk, and gene screening for women of childbearing age prior to pregnancy may help prevent NTDs induced by the risk allele. In addition, the consumption of alcohol, tea and coffee, and low intakes of fruit and vegetable are also associated with the increased risk of NTDs, and should be avoided by women of childbearing age.

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Section: B-vitamins One-carbon Metabolism and Ntdsmentioning

confidence: 99%

Nutrition, One-Carbon Metabolism and Neural Tube Defects: A Review

Wahlqvist

2016

Nutrients

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“…Based on the probable pathogenicity of rs1801394 in mediating NTD risk and to overcome the small sample size limitation in this study, we explored available data to estimate the extent of association between this variant and NTD patients in other populations. The MTRR mutant genotype has been suggested to increase the risk of NTD development in Canadians (Wilson et al, 1999), Han Chinese in Tianjin province, China (Fang et al, 2018;Wang et al, 2015), Polish (Pietrzyk et al, 2003), Hispanics (Zhu et al, 2003) and English (Doudney et al, 2009). Conversely, no associations were found in the Dutch (Brouns et al, 2008;van der Linden et al, 2006), Irish (O'Leary et al, 2005, Chinese in Liaoning province (Zhang et al, 2019) and central China (Liu et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

MTRR gene variant rs1801394 found in Malaysian patients with neural tube defects

et al. 2020

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Neural tube defects (NTDs) are congenital anomalies resulting from the failure of neural tube closure during embryogenesis. The precise molecular mechanisms underlying this multifactorial disease is poorly understood, although single nucleotide polymorphisms in genes involved in the one-carbon metabolism cycle are believed to contribute towards NTD development. Among them is 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR). Protein function prediction algorithms (PolyPhen-2, PROVEAN, SIFT, SMART-Ensembl) were employed to evaluate its pathogenicity potential caused by the replacement of isoleucine with methionine. Seven NTD patients and 12 of their parents were recruited for this study. DNA samples were collected through blood or saliva whereby the extracted DNAs were then sent for whole exome sequencing (WES). Zygosity of the variant was confirmed from WES data of each subject and further validated through polymerase chain reaction (PCR) and Sanger sequencing. The results revealed that 57% of patients and 83% of parents carried rs1801394 mutation in their MTRR gene, based on either homozygous (G/G) or heterozygous (A/G) genotypes. Bioinformatics analysis of this missense mutation predicted that this change is damaging to MTRR protein function by 2 of the 3 predictor algorithms and that the change from isoleucine to methionine amino acid affects flavodoxin domain of the protein. This impacts enzyme activity within the one-carbon metabolism pathway, which is linked to the aetiology of NTDs. From population databases, this variant was considered common with a MAF >0.3, however, it was not found in the Singapore Genome Variation Project (SGVP), whose population is a closer representation of the Malaysian subjects investigated here. Hence, we explored the prevalence of this variant in other studies and found that its association with NTDs differed across populations worldwide. Finally, we conclude that rs1801394 may be an NTD risk factor in the Malaysian population and should be further investigated as a potential prenatal screening tool.

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“…Más de 100 genes han sido investigados por su riesgo de asociación con espina bífida, incluidos aquellos relacionados con el metabolismo del ácido fólico, de la glucosa, ácido retinoide y de la apoptosis. Sin embargo, desconocemos cuántos genes pueden conferir riesgo de DTN en humanos (4,5) . La mayoría de los DTN consiste en malformaciones aisladas de origen multifactorial, aunque también pueden formar parte de un síndrome en asociación con desórdenes cromosómicos, como resultado de exposición a factores ambientales o a deficiencias de ácido fólico, uso de anticonvulsivantes como ácido valproico, antagonistas del ácido fólico tales como carbamazapina, fenobarbital, fenitoína, primadona, sulfasalazina, trimetroprim o metrotexato (6) .…”

Section: Discussionunclassified

Defecto amplio del tubo neural. A propósito de un caso

Quintero¹,

Salem²

2018

Rev peru ginecol obstet.

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Los defectos del tubo neural representan la segunda causa de malformación congénita más frecuentes del desarrollo prenatal y constituyen el 10% de las mismas. Su origen suele ser multifactorial, dando lugar a un cierre incompleto o defectuoso del neuroporo anterior y/o posterior, y ocasionando diferentes niveles de defectos en el sistema nervioso central. A pesar de toda la investigación realizada, nuestros conocimientos sobre la etiología genética de esta malformación son todavía muy limitados. Se desconoce cuántos genes pueden conferir riesgo de anomalía en el desarrollo del tubo neural. El diagnóstico se basa principalmente en el estudio ecográfico del sistema nervioso central en el segundo trimestre de la gestación, aunque su valoración en el primer trimestre nos permite una aproximación diagnóstica bastante confiable por la presencia de marcadores ecográficos descritos hace pocos años. Una vez confirmado el diagnóstico el manejo depende (en países como España en donde se permite el aborto) de la voluntad de los padres de continuar o no con la gestación; y en caso de continuar, existen opciones de tratamiento quirúrgico intrauterino o posterior al nacimiento. El pronóstico de esta malformación suele ser variable y depende de localización, tamaño y su asociación o no con hidrocefalia.

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Analysis of MTR and MTRR Polymorphisms for Neural Tube Defects Risk Association

Cited by 17 publications

References 34 publications

Nutrition, One-Carbon Metabolism and Neural Tube Defects: A Review

Nutrition, One-Carbon Metabolism and Neural Tube Defects: A Review

MTRR gene variant rs1801394 found in Malaysian patients with neural tube defects

Defecto amplio del tubo neural. A propósito de un caso

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