This research was supported by grants from the NIH/NHLBI (P50 HL74731 and R01 HL076773 to E.G. and L.E.M.). This project was also supported by grant M01-RR-000240 and UL1-RR-024134 from the National Center for Research Resources.
NAT1,NOS3, and TYMS genotypes and the risk of conotruncal cardiac defects†
Article first published online: 1 DEC 2010
Copyright © 2010 Wiley-Liss, Inc.
Birth Defects Research Part A: Clinical and Molecular Teratology
Volume 91, Issue 1, pages 61–65, January 2011
How to Cite
Lupo, P. J., Mitchell, L. E. and Goldmuntz, E. (2011), NAT1,NOS3, and TYMS genotypes and the risk of conotruncal cardiac defects. Birth Defects Research Part A: Clinical and Molecular Teratology, 91: 61–65. doi: 10.1002/bdra.20745
- Issue published online: 19 JAN 2011
- Article first published online: 1 DEC 2010
- Manuscript Accepted: 2 SEP 2010
- Manuscript Revised: 31 AUG 2010
- Manuscript Received: 24 JUN 2010
- NIH/NHLBI. Grant Number: P50 HL74731 and R01 HL076773
- National Center for Research Resources.. Grant Numbers: M01-RR-000240, UL1-RR-024134
- NAT1 gene;
- NOS3 gene;
- TYMS gene;
- conotruncal cardiac defects
Although congenital heart defects (CHDs) are a common and serious group of birth defects, relatively little is known about the causes of these conditions, and there are no established prevention strategies. There is, however, evidence suggesting that the risk of CHDs in general, and conotruncal and related defects (CTRDs) in particular, may be associated with maternal folate status and genetic variants of folate-related genes. Although several folate-related genes have been studied as they relate to CHDs and CTRDs (e.g., MTHFR), others have not been adequately assessed.
Case-parent triads were examined using log-linear analyses to assess the associations between CTRDs and both the genotype inherited by the case and the maternal genotype for the following variants: NAT1 1095C>A, NOS3 894G>T, and TYMS 1494del6. Subgroup analyses were also conducted among cases with classic conotruncal defects and cases with normally related great arteries.
The results provided little evidence that CTRD risk was associated with the genotype inherited by the case for any of the analyzed variants. However, our results suggest that CTRD risk may be associated with the maternal genotype for NOS3 894G>T (p = 0.024 in the subgroup with normally related great arteries) and TYMS 1494del6 (p = 0.048 in the subgroup with classicconotruncal defects). However, these results were not significant after correcting for multiple comparisons.
This study provides further evidence that CTRD risk may be related to variation within folate-pathway genes and suggests that these associations are, at least in part, mediated through the maternal genotype. Birth Defects Research (Part A), 2011. © 2010 Wiley-Liss, Inc.