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Open Access 01-12-2009 | Research article

118 SNPs of folate-related genes and risks of spina bifida and conotruncal heart defects

Authors: Gary M Shaw, Wei Lu, Huiping Zhu, Wei Yang, Farren BS Briggs, Suzan L Carmichael, Lisa F Barcellos, Edward J Lammer, Richard H Finnell

Published in: BMC Medical Genetics | Issue 1/2009

Abstract

Background

Folic acid taken in early pregnancy reduces risks for delivering offspring with several congenital anomalies. The mechanism by which folic acid reduces risk is unknown. Investigations into genetic variation that influences transport and metabolism of folate will help fill this data gap. We focused on 118 SNPs involved in folate transport and metabolism.

Methods

Using data from a California population-based registry, we investigated whether risks of spina bifida or conotruncal heart defects were influenced by 118 single nucleotide polymorphisms (SNPs) associated with the complex folate pathway. This case-control study included 259 infants with spina bifida and a random sample of 359 nonmalformed control infants born during 1983–86 or 1994–95. It also included 214 infants with conotruncal heart defects born during 1983–86. Infant genotyping was performed blinded to case or control status using a designed SNPlex assay. We examined single SNP effects for each of the 118 SNPs, as well as haplotypes, for each of the two outcomes.

Results

Few odds ratios (ORs) revealed sizable departures from 1.0. With respect to spina bifida, we observed ORs with 95% confidence intervals that did not include 1.0 for the following SNPs (heterozygous or homozygous) relative to the reference genotype: BHMT (rs3733890) OR = 1.8 (1.1–3.1), CBS (rs2851391) OR = 2.0 (1.2–3.1); CBS (rs234713) OR = 2.9 (1.3–6.7); MTHFD1 (rs2236224) OR = 1.7 (1.1–2.7); MTHFD1 (hcv11462908) OR = 0.2 (0–0.9); MTHFD2 (rs702465) OR = 0.6 (0.4–0.9); MTHFD2 (rs7571842) OR = 0.6 (0.4–0.9); MTHFR (rs1801133) OR = 2.0 (1.2–3.1); MTRR (rs162036) OR = 3.0 (1.5–5.9); MTRR (rs10380) OR = 3.4 (1.6–7.1); MTRR (rs1801394) OR = 0.7 (0.5–0.9); MTRR (rs9332) OR = 2.7 (1.3–5.3); TYMS (rs2847149) OR = 2.2 (1.4–3.5); TYMS (rs1001761) OR = 2.4 (1.5–3.8); and TYMS (rs502396) OR = 2.1 (1.3–3.3). However, multiple SNPs observed for a given gene showed evidence of linkage disequilibrium indicating that the observed SNPs were not individually contributing to risk. We did not observe any ORs with confidence intervals that did not include 1.0 for any of the studied SNPs with conotruncal heart defects. Haplotype reconstruction showed statistical evidence of nonrandom associations with TYMS, MTHFR, BHMT and MTR for spina bifida.

Conclusion

Our observations do not implicate a particular folate transport or metabolism gene to be strongly associated with risks for spina bifida or conotruncal defects.

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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2350/10/49/prepub

Title: 118 SNPs of folate-related genes and risks of spina bifida and conotruncal heart defects
Authors: Gary M Shaw
Wei Lu
Huiping Zhu
Wei Yang
Farren BS Briggs
Suzan L Carmichael
Lisa F Barcellos
Edward J Lammer
Richard H Finnell
Publication date: 01-12-2009
Publisher: BioMed Central
Published in: BMC Medical Genetics / Issue 1/2009
Electronic ISSN: 1471-2350
DOI: https://doi.org/10.1186/1471-2350-10-49

Keynote webinar | Spotlight on medication adherence

Springer Medicine

118 SNPs of folate-related genes and risks of spina bifida and conotruncal heart defects

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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