Jensen Liselotte E, Hoess Katy, Whitehead Alexander S, Mitchell Laura E
Department of Pharmacology and Center for Pharmacogenetics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Birth Defects Res A Clin Mol Teratol. 2005 Jul;73(7):512-6. doi: 10.1002/bdra.20143.
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.
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.
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.
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.
通过孕期补充叶酸可降低胎儿患神经管缺陷（NTD）的风险，但其潜在的叶酸依赖保护机制仍不清楚。N - 乙酰基转移酶1参与芳香族和杂环胺的乙酰化以及叶酸的分解代谢。因此，编码N - 乙酰基转移酶1的基因NAT1中的功能多态性可能是神经管缺陷的危险因素。这些变体可能通过其在乙酰化或叶酸分解代谢中的作用影响神经管缺陷的风险，并可能通过母体或胚胎基因型起作用。
作为一项关于脊柱裂的家庭研究的一部分，获取了NAT1 C1095A基因型以及孕期母体多种维生素使用情况和吸烟信息。使用对数线性模型评估脊柱裂与胚胎和母体NAT1 C1095A基因型之间的关联，以及潜在的NAT1 C1095A基因型 - 暴露相互作用。
分析没有提供证据表明胚胎或母体的NAT1 C1095基因型独立影响脊柱裂风险，或通过与母体使用多种维生素的相互作用来影响。有证据表明胚胎以及可能母体的NAT1 C1095A基因型通过与母体吸烟状况的相互作用影响脊柱裂风险。
NAT1 C1095A多态性的基因型似乎不是脊柱裂的独立危险因素。然而，这些分析结果提供了初步证据，表明这种多态性可能与孕早期吸烟女性后代患脊柱裂的风险有关。
