Get access
Advertisement

The NAT1 C1095A polymorphism, maternal multivitamin use and smoking, and the risk of spina bifida

Authors

  • Liselotte E. Jensen,

    1. Department of Pharmacology and Center for Pharmacogenetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
    Search for more papers by this author
  • Katy Hoess,

    1. Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
    Search for more papers by this author
  • Alexander S. Whitehead,

    1. Department of Pharmacology and Center for Pharmacogenetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
    Search for more papers by this author
  • Laura E. Mitchell

    Corresponding author
    1. Institute of Biosciences and Technology, The Texas A&M University System Health Science Center, Houston, Texas
    • Institute of Biosciences and Technology, The Texas A&M University System Health Science Center, 2121 W. Holcombe Blvd., Houston, TX 77030
    Search for more papers by this author

  • This study was approved by the Institutional Review Boards of The Texas A&M University, The University of Pennsylvania School of Medicine, and each of the participating hospitals. Informed consent and, when appropriate, assent, was/were obtained for each study subject.

Abstract

BACKGROUND

The risk of having a child with a neural tube defect (NTD) can be reduced by maternal, periconceptional supplementation with folic acid, but the underlying folate-dependent protective mechanism remains unclear. N-acetyltransferase 1 is involved in acetylation of aromatic and heterocyclic amines and the catabolism of folates. Hence, functional polymorphisms in NAT1, the gene encoding N-acetyltransferase 1, are plausible risk factors for NTDs. Such variants could exert an influence on the risk of NTDs via their role in acetylation or folate catabolism and could act through the maternal or the embryonic genotype.

METHODS

NAT1 C1095A genotypes and information on maternal, periconceptional multivitamin use and smoking were obtained as part of a family-based study of spina bifida. Associations between spina bifida and the embryonic and maternal NAT1 C1095A genotypes, and potential NAT1 C1095A genotype–exposure interactions were evaluated using log-linear modeling.

RESULTS

The analyses provided no evidence that the embryonic or maternal NAT1 C1095 genotypes influence the risk of spina bifida independently, or through interactions with maternal use of multivitamins. There was evidence that the embryonic, and possibly the maternal, NAT1 C1095A genotype influence the risk of spina bifida via interactions with maternal smoking status.

CONCLUSIONS

The genotype for the NAT1 C1095A polymorphism does not appear to be an independent risk factor for spina bifida. However, the results of these analyses provide preliminary evidence that this polymorphism may be associated with the risk of spina bifida in the offspring of women who smoke during early pregnancy. Birth Defects Research (Part A), 2005. © 2005 Wiley-Liss, Inc.

Get access to the full text of this article

Ancillary