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NAT1,NOS3, and TYMS genotypes and the risk of conotruncal cardiac defects

Authors

  • Philip J. Lupo,

    1. Human Genetics Center, Division of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston, Texas
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  • Laura E. Mitchell,

    1. Human Genetics Center, Division of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston, Texas
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  • Elizabeth Goldmuntz

    Corresponding author
    1. Division of Cardiology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
    • Division of Cardiology, Children's Hospital of Philadelphia, Abramson Research Center 702A, 3615 Civic Center Boulevard, Philadelphia, PA 19104-4318
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  • 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.

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

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