Abstract
Neural tube defects are the most common congenital disorders associated with malformations of the spinal cord and skull, such as anencephaly, craniorachischisis, spina bifida cystica, encephalocele, and spina bifida occulta. They arise as a consequence of improper closure of the neural tube during embryogenesis.
These are multifactorial diseases with risk factors including genetic predisposition, various environmental exposures, gender differences, and racial diversity. One of the key risk factors is low periconceptional folate intake in women of reproductive age.
The aim: Given that the pathophysiology of neural tube defects and folate metabolism is still poorly understood and elucidated. Our work focuses on the recent insights from research on one-carbon metabolism and single nucleotide polymorphisms of genes in the folate pathway on the development of neural tube defects and other diseases. It appears that the demand for carbon units is highest during fetal development. Folate deficiency causes hypomethylation of deoxyribonucleic acid, blocks synthesis of 2´- deoxythymidine - 5´- monophosphate, and increases misincorporation of uracil. These effects can result in genomic instabilities that increase the risk of neural tube defects.
Results: Identifying genetic risk factors for neural tube defects is not straightforward due to the involvement of multiple genes in the neural tube closure process. Studies of genetic polymorphisms suggest risk factors, but no specific folate-related gene has yet been identified as a major determinant of the possibility of developing neural tube defects.
Conclusion: In the future, it will be necessary to use new technologies to evaluate multiple genes, including folate-related genes and other genes in the same individuals, to reveal the possible combined association of risk alleles that may not be individually statistically significant. Current advances in whole-genome, exome, and next-generation sequencing may help to understand the genetic and epigenetic basis of neural tube defects in humans. The use of transcriptomics, proteomics, and metabolomics may help in the identification of new biomarkers and molecular networks related to neural tube defects (Fig. 1, Ref. 71). Text in PDF www.lekarsky.herba.sk.
KEY WORDS: neural tube defects, anencephaly, craniorachischisis, spina bifida, encephalocele, folic acid, folate, 5-methyltetrahydrofolate, gene polymorphisms, epigenomics.
Lek Obz 2024, 73 (7): 248-256
Vanda RÍSOVÁ 1, Petra OŤAPKOVÁ 2, Ján MIERTUŠ 3, Lívia GAJDOŠOVÁ 4, Vladimír JAKUŠ 4, Štefan POLÁK 5
1 Ústav histológie a embryológie LF UK v Bratislave, prednosta prof. RNDr. I. Varga, PhD. et PhD.
2 II. gynekologicko-pôrodnícka klinika LF UK a UN v Bratislave, prednosta prof. MUDr. J. Záhumenský, PhD., MPH
3 Magis Lab SRL, Rovereto (TN), Italy, prednosta M. Bertelli
4 Ústav lekárskej chémie, biochémie a klinickej biochémie LF UK v Bratislave, prednosta prof. MUDr. L. Turecký, CSc.
5 Anatomický ústav LF UK v Bratislave, prednosta prof. MUDr. Š. Polák, CSc.
