Neural tube defects and disturbed maternal folate- and homocysteine-mediated one-carbon metabolism

Disturbances in maternal folate and homocysteine metabolism are associated with neural tube defects (NTDs). However, the role played by specific components in the one-carbon metabolic pathways leading to NTDs remains unclear. Here, we conducted a case-control study to investigate the relationship be...

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Bibliographic Details
Published in:Experimental neurology 2008-08, Vol.212 (2), p.515-521
Main Authors: Zhang, Hong-Yang, Luo, Guo-An, Liang, Qiong-Lin, Wang, Yong, Yang, Hui-Hua, Wang, Yi-Ming, Zheng, Xiao-Ying, Song, Xin-Ming, Chen, Gong, Zhang, Ting, Wu, Jian-Xin
Format: Article
Language:English
Subjects:
5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase - blood
Adolescent
Adult
Biological and medical sciences
Carbon - metabolism
Case-Control Studies
Chi-Square Distribution
Chromatography - methods
Development. Senescence. Regeneration. Transplantation
Female
Folate
Folic Acid - blood
Fundamental and applied biological sciences. Psychology
Homocysteine
Homocysteine - blood
Humans
Maternal Age
Medical sciences
Models, Biological
Neural tube defects
Neural Tube Defects - metabolism
Neurology
One-carbon metabolism
Pathogenesis
Potential risk factors
Pregnancy
S-Adenosylhomocysteine - blood
Vertebrates: nervous system and sense organs
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Summary:Disturbances in maternal folate and homocysteine metabolism are associated with neural tube defects (NTDs). However, the role played by specific components in the one-carbon metabolic pathways leading to NTDs remains unclear. Here, we conducted a case-control study to investigate the relationship between the disturbed one-carbon metabolism and the risk of NTD-affected pregnancies. Major components were examined in population-based samples of women who had NTD-affected pregnancies (case subjects, n = 46) or unaffected by any birth defects (control subjects, n = 44). We used the newly developed high-performance liquid chromatography tandem mass spectrometry along with a routine chemiluminescent assay, to measure serum concentrations of 5-methyltetrahydrofolate (5-MeTHF), 5-formyltetrahydrofolate (5-FoTHF), folic acid, serine, histidine, homocysteine, cystathionine, methionine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), total folate and vitamin B12 in both groups adjusting for lifestyle and sociodemographic variables. We found significantly lower serum concentrations of 5-MeTHF ( P < 0.001), 5-FoTHF ( P = 0.004), total folate ( P < 0.001) and vitamin B12 ( P = 0.005) and remarkably higher concentrations of SAH ( P = 0.016) in cases than in controls. Therefore, these compounds could be identified as potential risk factors for NTD's early diagnosis. Further analysis of relevant genetic and epidemiologic investigations may provide more insights into the pathogenesis of NTDs and enhance current nutritional intervention strategies to reduce the risk of NTD-affected pregnancies.
ISSN:0014-4886
1090-2430
DOI:10.1016/j.expneurol.2008.04.044