Folate-related gene variants in Irish families affected by neural tube defects
Periconceptional folic acid use can often prevent neural tube defects (NTDs). Variants of genes involved in folate metabolism in mothers and children have been associated with occurrence of NTDs. We identified Irish families with individuals affected by neural tube defects. In these families, we ob...
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doaj-27bb9b5cf459460a849183a80367239d2020-11-24T22:53:39ZengFrontiers Media S.A.Frontiers in Genetics1664-80212013-11-01410.3389/fgene.2013.0022362062Folate-related gene variants in Irish families affected by neural tube defectsRidgely eFisk Green0Julianne eByrne1Krista S. Crider2Margaret eGallagher3Deborah eKoontz4Robert J. Berry5Carter Consulting, Inc. and National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and PreventionBoyne Research InstituteCenters for Disease Control and Prevention, Atlanta, GA, USACenters for Disease Control and PreventionCenters for Disease Control and PreventionCenters for Disease Control and Prevention, Atlanta, GA, USAPericonceptional folic acid use can often prevent neural tube defects (NTDs). Variants of genes involved in folate metabolism in mothers and children have been associated with occurrence of NTDs. We identified Irish families with individuals affected by neural tube defects. In these families, we observed that neural tube defects and birth defects overall occurred at a higher rate in the maternal lineage compared with the paternal lineage. The goal of this study was to look for evidence for genetic effects that could explain the discrepancy in the occurrence of these birth defects in the maternal vs. paternal lineage. We genotyped blood samples from 322 individuals from NTD-affected Irish families, identified through their membership in spina bifida associations. We looked for differences in distribution in maternal vs. paternal lineages of five genetic polymorphisms: the DHFR 19bp deletion, MTHFD1 1958G>A, MTHFR 1298A>C, MTHFR 677C>T, and SLC19A1 80A>G. In addition to looking at genotypes individually, we determined the number of genotypes associated with decreased folate metabolism in each relative (risk genotypes) and compared the distribution of these genotypes in maternal vs. paternal relatives. Overall, maternal relatives had a higher number of genotypes associated with lower folate metabolism than paternal relatives (p=0.017). We expected that relatives would share the same risk genotype as the individuals with NTDs and/or their mothers. However, we observed that maternal relatives had an over-abundance of any risk genotype, rather than one specific genotype. The observed genetic effects suggest an epigenetic mechanism in which decreased folate metabolism results in epigenetic alterations related to the increased rate of NTDs and other birth defects seen in the maternal lineage. Future studies on the etiology of NTDs and other birth defects could benefit from including multigenerational extended families, in order to explore potential epigenetic mechanisms.http://journal.frontiersin.org/Journal/10.3389/fgene.2013.00223/fullNeural Tube Defectsfolate metabolismDHFR 19bp deletionMTHFD1 1958G>AMTHFR 1298A>CMTHFR 677C>T |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ridgely eFisk Green Julianne eByrne Krista S. Crider Margaret eGallagher Deborah eKoontz Robert J. Berry |
spellingShingle |
Ridgely eFisk Green Julianne eByrne Krista S. Crider Margaret eGallagher Deborah eKoontz Robert J. Berry Folate-related gene variants in Irish families affected by neural tube defects Frontiers in Genetics Neural Tube Defects folate metabolism DHFR 19bp deletion MTHFD1 1958G>A MTHFR 1298A>C MTHFR 677C>T |
author_facet |
Ridgely eFisk Green Julianne eByrne Krista S. Crider Margaret eGallagher Deborah eKoontz Robert J. Berry |
author_sort |
Ridgely eFisk Green |
title |
Folate-related gene variants in Irish families affected by neural tube defects |
title_short |
Folate-related gene variants in Irish families affected by neural tube defects |
title_full |
Folate-related gene variants in Irish families affected by neural tube defects |
title_fullStr |
Folate-related gene variants in Irish families affected by neural tube defects |
title_full_unstemmed |
Folate-related gene variants in Irish families affected by neural tube defects |
title_sort |
folate-related gene variants in irish families affected by neural tube defects |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Genetics |
issn |
1664-8021 |
publishDate |
2013-11-01 |
description |
Periconceptional folic acid use can often prevent neural tube defects (NTDs). Variants of genes involved in folate metabolism in mothers and children have been associated with occurrence of NTDs. We identified Irish families with individuals affected by neural tube defects. In these families, we observed that neural tube defects and birth defects overall occurred at a higher rate in the maternal lineage compared with the paternal lineage. The goal of this study was to look for evidence for genetic effects that could explain the discrepancy in the occurrence of these birth defects in the maternal vs. paternal lineage. We genotyped blood samples from 322 individuals from NTD-affected Irish families, identified through their membership in spina bifida associations. We looked for differences in distribution in maternal vs. paternal lineages of five genetic polymorphisms: the DHFR 19bp deletion, MTHFD1 1958G>A, MTHFR 1298A>C, MTHFR 677C>T, and SLC19A1 80A>G. In addition to looking at genotypes individually, we determined the number of genotypes associated with decreased folate metabolism in each relative (risk genotypes) and compared the distribution of these genotypes in maternal vs. paternal relatives. Overall, maternal relatives had a higher number of genotypes associated with lower folate metabolism than paternal relatives (p=0.017). We expected that relatives would share the same risk genotype as the individuals with NTDs and/or their mothers. However, we observed that maternal relatives had an over-abundance of any risk genotype, rather than one specific genotype. The observed genetic effects suggest an epigenetic mechanism in which decreased folate metabolism results in epigenetic alterations related to the increased rate of NTDs and other birth defects seen in the maternal lineage. Future studies on the etiology of NTDs and other birth defects could benefit from including multigenerational extended families, in order to explore potential epigenetic mechanisms. |
topic |
Neural Tube Defects folate metabolism DHFR 19bp deletion MTHFD1 1958G>A MTHFR 1298A>C MTHFR 677C>T |
url |
http://journal.frontiersin.org/Journal/10.3389/fgene.2013.00223/full |
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