Journal article
Conotruncal heart defects and common variants in maternal and fetal genes in folate, homocysteine, and transsulfuration pathways
Birth defects research. A Clinical and molecular teratology, Vol.100(2), pp.116-126
02/2014
DOI: 10.1002/bdra.23225
PMCID: PMC4118819
PMID: 24535845
Abstract
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 transsulfuration 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 2008. DNA samples from 616 case‐parental triads affected by CTDs and 1645 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 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 Bayesian false‐discovery probability (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 nine fetal SNPs had a Bayesian false‐discovery probability <0.8 for gene‐by‐environment (G × E) interactions with maternal folic acid supplementation.
Conclusion
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. Birth Defects Research (Part A) 100:116–126, 2014. © 2014 Wiley Periodicals, Inc.
Details
- Title: Subtitle
- Conotruncal heart defects and common variants in maternal and fetal genes in folate, homocysteine, and transsulfuration pathways
- Creators
- Charlotte A Hobbs - Arkansas Children's Hospital Research InstituteMario A Cleves - Arkansas Children's Hospital Research InstituteStewart L MacLeod - Arkansas Children's Hospital Research InstituteStephen W Erickson - Arkansas Children's Hospital Research InstituteXinyu Tang - Arkansas Children's Hospital Research InstituteJingyun Li - Arkansas Children's Hospital Research InstituteMing Li - Arkansas Children's Hospital Research InstituteTodd Nick - Arkansas Children's Hospital Research InstituteSadia Malik - Arkansas Children's Hospital Research InstituteNational Birth Defects Prevention Study
- Contributors
- Paul A Romitti (Contributor) - University of Iowa, Epidemiology
- Resource Type
- Journal article
- Publication Details
- Birth defects research. A Clinical and molecular teratology, Vol.100(2), pp.116-126
- DOI
- 10.1002/bdra.23225
- PMID
- 24535845
- PMCID
- PMC4118819
- NLM abbreviation
- Birth Defects Res A Clin Mol Teratol
- ISSN
- 1542-0752
- eISSN
- 1542-0760
- Publisher
- Wiley
- Number of pages
- 11
- Language
- English
- Date published
- 02/2014
- Academic Unit
- Epidemiology; Biostatistics
- Record Identifier
- 9984214664002771
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