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One-carbon metabolism and global DNA methylation in mothers of individuals with Down syndrome.
- Source :
-
Human cell [Hum Cell] 2021 Nov; Vol. 34 (6), pp. 1671-1681. Date of Electronic Publication: 2021 Aug 19. - Publication Year :
- 2021
-
Abstract
- Down syndrome (DS) is the most common chromosomal disorder, resulting from the failure of normal chromosome 21 segregation. Studies have suggested that impairments within the one-carbon metabolic pathway can be of relevance for the global genome instability observed in mothers of individuals with DS. Based on the association between global DNA hypomethylation, genome instability, and impairments within the one-carbon metabolic pathway, the present study aimed to identify possible predictors, within the one-carbon metabolism, of global DNA methylation, measured by methylation patterns of LINE-1 and Alu repetitive sequences, in mothers of individuals with DS and mothers of individuals without the syndrome. In addition, we investigated one-carbon genetic polymorphisms and metabolites as maternal predisposing factors for the occurrence of trisomy 21 in children. Eighty-three samples of mothers of children with DS with karyotypically confirmed free trisomy 21 (case group) and 84 of mothers who had at least one child without DS or any other aneuploidy were included in the study. Pyrosequencing assays were performed to access global methylation. The results showed that group affiliation (case or control), betaine-homocysteine methyltransferase (BHMT) G742A and transcobalamin 2 (TCN2) C776G polymorphisms, and folate concentration were identified as predictors of global Alu DNA methylation values. In addition, thymidylate synthase (TYMS) 28-bp repeats 2R/3R or 3R/3R genotypes are independent maternal predisposing factors for having a child with DS. This study adds evidence that supports the association of impairments in the one-carbon metabolism, global DNA methylation, and the possibility of having a child with DS.<br /> (© 2021. Japan Human Cell Society.)
- Subjects :
- Adolescent
Adult
Aged
Alu Elements genetics
Betaine-Homocysteine S-Methyltransferase genetics
Betaine-Homocysteine S-Methyltransferase metabolism
Female
Folic Acid metabolism
Genetic Predisposition to Disease genetics
Humans
Long Interspersed Nucleotide Elements genetics
Male
Middle Aged
Polymorphism, Genetic
Signal Transduction genetics
Signal Transduction physiology
Thymidylate Synthase genetics
Transcobalamins genetics
Transcobalamins metabolism
Young Adult
Carbon metabolism
DNA Methylation genetics
Down Syndrome genetics
Down Syndrome metabolism
Genome-Wide Association Study
Genomic Instability genetics
Mother-Child Relations
Mothers
Subjects
Details
- Language :
- English
- ISSN :
- 1749-0774
- Volume :
- 34
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Human cell
- Publication Type :
- Academic Journal
- Accession number :
- 34410622
- Full Text :
- https://doi.org/10.1007/s13577-021-00586-0