The NAT1 C1095A polymorphism, maternal multivitamin use and smoking, and the risk of spina bifida.
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.
Jensen
Liselotte E
LE
Department of Pharmacology and Center for Pharmacogenetics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Hoess
Katy
K
Whitehead
Alexander S
AS
Mitchell
Laura E
LE
D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007527:Isoenzymes; D011110:Polymorphism, Genetic; D016742:Preconception Care; D011247:Pregnancy; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D016135:Spinal Dysraphism / Q000453:epidemiology / Q000235:genetics*; D014815:Vitamins / Q000627:therapeutic use*
D007527:Isoenzymes; D014815:Vitamins; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1