Details:

Alternative Title:
Birth Defects Res A Clin Mol Teratol
Personal Author:
Hobbs, Charlotte A. ; Cleves, Mario A. ; MacLeod, Stewart L. ; Erickson, Stephen W. ; Tang, Xinyu ; ... More +
Hobbs, Charlotte A. ; Cleves, Mario A. ; MacLeod, Stewart L. ; Erickson, Stephen W. ; Tang, Xinyu ; Li, Jingyun ; Li, Ming ; Nick, Todd ; Malik, Sadia Less -
Corporate Authors:
National Birth Defects Prevention Study
Description:
Background

We investigated the association between conotruncal heart defects (CTDs) and maternal and fetal single nucleotide polymorphisms (SNPs) in 60 genes in the folate, homocysteine and pathways. We also investigated whether periconceptional maternal folic acid supplementation modified associations between CTDs and SNPs.

Methods

Participants were enrolled in the National Birth Defects Prevention Study between 1997 and 2007. DNA samples from 616 case-parental triads affected by CTDs and 1,645 control-parental triads were genotyped using an Illumina® Golden Gate custom SNP panel. A hybrid design analysis, optimizing data from case and control trios, was used to identify maternal and fetal SNPs associated with CTDs.

Results

Among 921 SNPs, 17 maternal and 17 fetal SNPs had a Bayesian false-discovery probability (BFDP) of <0.8. Ten of the 17 maternal SNPs and 2 of the 17 fetal SNPs were found within the glutamate-cysteine ligase, catalytic subunit (GCLC) gene. Fetal SNPs with the lowest BFDP (rs2612101, rs2847607, rs2847326, rs2847324) were found within the thymidylate synthetase (TYMS) gene. Additional analyses indicated that the risk of CTDs associated with candidate SNPs was modified by periconceptional folic acid supplementation. Nineteen maternal and 9 fetal SNPs had BFDP <0.8 for gene-by-environment (GxE) interactions with maternal folic acid supplementation.

Conclusions

These results support previous studies suggesting that maternal and fetal SNPs within folate, homocysteine and transsulfuration pathways are associated with CTD risk. Maternal use of supplements containing folic acid may modify the impact of SNPs on the developing heart.


Subjects:
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Adult Article Bayes Theorem Case-Control Studies Conotruncal Heart Defects Dietary Supplements Female Folic Acid Genetics Gene X Environment Interaction Glutamate-Cysteine Ligase Heart Defects, Congenital Homocysteine Humans Infant, Newborn Oxidative Stress Polymorphism, Single Nucleotide Pregnancy Prospective Studies Risk Factors Single Nucleotide Polymorphisms Thymidylate Synthase
Source:
Birth Defects Res A Clin Mol Teratol. 100(2):116-126.
Pubmed ID:
24535845
Pubmed Central ID:
PMC4118819
Document Type:
Journal Article
Funding:
5R01HD039054-12/HD/NICHD NIH HHS/United States ; 5U01DD000491-05/DD/NCBDD CDC HHS/United States ; R01 HD039054/HD/NICHD NIH HHS/United States
5R01HD039054-12/HD/NICHD NIH HHS/United States ; 5U01DD000491-05/DD/NCBDD CDC HHS/United States ; R01 HD039054/HD/NICHD NIH HHS/United States Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:fe2ddf14f9c1a5965561010c56d3558c0b2faee7cfc0838b8e6b5e47af9b5369
Download URL:
https://stacks.cdc.gov/view/cdc/30057/cdc_30057_DS1.pdf
File Type:

Supporting Files

• 	NIHMS597772-supplement-Supp_TableS1.xlsx	xlsx
  	nihms597772.nxml	txt
  	nihms597772f1.gif	gif
  	nihms597772f1.jpg	jpeg
  	nihms597772f2.gif	gif
  	nihms597772f2.jpg	jpeg

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