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Profiling placental and fetal DNA methylation in human neural tube defects

BACKGROUND: The incidence of neural tube defects (NTDs) declined by about 40 % in Canada with the introduction of a national folic acid (FA) fortification program. Despite the fact that few Canadians currently exhibit folate deficiency, NTDs are still the second most common congenital abnormality. F...

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Autores principales: Price, E. Magda, Peñaherrera, Maria S., Portales-Casamar, Elodie, Pavlidis, Paul, Van Allen, Margot I., McFadden, Deborah E., Robinson, Wendy P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756451/
https://www.ncbi.nlm.nih.gov/pubmed/26889207
http://dx.doi.org/10.1186/s13072-016-0054-8
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author Price, E. Magda
Peñaherrera, Maria S.
Portales-Casamar, Elodie
Pavlidis, Paul
Van Allen, Margot I.
McFadden, Deborah E.
Robinson, Wendy P.
author_facet Price, E. Magda
Peñaherrera, Maria S.
Portales-Casamar, Elodie
Pavlidis, Paul
Van Allen, Margot I.
McFadden, Deborah E.
Robinson, Wendy P.
author_sort Price, E. Magda
collection PubMed
description BACKGROUND: The incidence of neural tube defects (NTDs) declined by about 40 % in Canada with the introduction of a national folic acid (FA) fortification program. Despite the fact that few Canadians currently exhibit folate deficiency, NTDs are still the second most common congenital abnormality. FA fortification may have aided in reducing the incidence of NTDs by overcoming abnormal one carbon metabolism cycling, the process which provides one carbon units for methylation of DNA. We considered that NTDs persisting in a folate-replete population may also occur in the context of FA-independent compromised one carbon metabolism, and that this might manifest as abnormal DNA methylation (DNAm). Second trimester human placental chorionic villi, kidney, spinal cord, brain, and muscle were collected from 19 control, 22 spina bifida, and 15 anencephalic fetuses in British Columbia, Canada. DNA was extracted, assessed for methylenetetrahydrofolate reductase (MTHFR) genotype and for genome-wide DNAm using repetitive elements, in addition to the Illumina Infinium HumanMethylation450 (450k) array. RESULTS: No difference in repetitive element DNAm was noted between NTD status groups. Using a false discovery rate <0.05 and average group difference in DNAm ≥0.05, differentially methylated array sites were identified only in (1) the comparison of anencephaly to controls in chorionic villi (n = 4 sites) and (2) the comparison of spina bifida to controls in kidney (n = 3342 sites). CONCLUSIONS: We suggest that the distinctive DNAm of spina bifida kidneys may be consequent to the neural tube defect or reflective of a common etiology for abnormal neural tube and renal development. Though there were some small shifts in DNAm in the other tested tissues, our data do not support the long-standing hypothesis of generalized altered genome-wide DNAm in NTDs. This finding may be related to the fact that most Canadians are not folate deficient, but it importantly opens the field to the investigation of other epigenetic and non-epigenetic mechanisms in the etiology of NTDs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13072-016-0054-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-47564512016-02-18 Profiling placental and fetal DNA methylation in human neural tube defects Price, E. Magda Peñaherrera, Maria S. Portales-Casamar, Elodie Pavlidis, Paul Van Allen, Margot I. McFadden, Deborah E. Robinson, Wendy P. Epigenetics Chromatin Research BACKGROUND: The incidence of neural tube defects (NTDs) declined by about 40 % in Canada with the introduction of a national folic acid (FA) fortification program. Despite the fact that few Canadians currently exhibit folate deficiency, NTDs are still the second most common congenital abnormality. FA fortification may have aided in reducing the incidence of NTDs by overcoming abnormal one carbon metabolism cycling, the process which provides one carbon units for methylation of DNA. We considered that NTDs persisting in a folate-replete population may also occur in the context of FA-independent compromised one carbon metabolism, and that this might manifest as abnormal DNA methylation (DNAm). Second trimester human placental chorionic villi, kidney, spinal cord, brain, and muscle were collected from 19 control, 22 spina bifida, and 15 anencephalic fetuses in British Columbia, Canada. DNA was extracted, assessed for methylenetetrahydrofolate reductase (MTHFR) genotype and for genome-wide DNAm using repetitive elements, in addition to the Illumina Infinium HumanMethylation450 (450k) array. RESULTS: No difference in repetitive element DNAm was noted between NTD status groups. Using a false discovery rate <0.05 and average group difference in DNAm ≥0.05, differentially methylated array sites were identified only in (1) the comparison of anencephaly to controls in chorionic villi (n = 4 sites) and (2) the comparison of spina bifida to controls in kidney (n = 3342 sites). CONCLUSIONS: We suggest that the distinctive DNAm of spina bifida kidneys may be consequent to the neural tube defect or reflective of a common etiology for abnormal neural tube and renal development. Though there were some small shifts in DNAm in the other tested tissues, our data do not support the long-standing hypothesis of generalized altered genome-wide DNAm in NTDs. This finding may be related to the fact that most Canadians are not folate deficient, but it importantly opens the field to the investigation of other epigenetic and non-epigenetic mechanisms in the etiology of NTDs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13072-016-0054-8) contains supplementary material, which is available to authorized users. BioMed Central 2016-02-16 /pmc/articles/PMC4756451/ /pubmed/26889207 http://dx.doi.org/10.1186/s13072-016-0054-8 Text en © Price et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Price, E. Magda
Peñaherrera, Maria S.
Portales-Casamar, Elodie
Pavlidis, Paul
Van Allen, Margot I.
McFadden, Deborah E.
Robinson, Wendy P.
Profiling placental and fetal DNA methylation in human neural tube defects
title Profiling placental and fetal DNA methylation in human neural tube defects
title_full Profiling placental and fetal DNA methylation in human neural tube defects
title_fullStr Profiling placental and fetal DNA methylation in human neural tube defects
title_full_unstemmed Profiling placental and fetal DNA methylation in human neural tube defects
title_short Profiling placental and fetal DNA methylation in human neural tube defects
title_sort profiling placental and fetal dna methylation in human neural tube defects
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756451/
https://www.ncbi.nlm.nih.gov/pubmed/26889207
http://dx.doi.org/10.1186/s13072-016-0054-8
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