The NAT1 C1095A polymorphism, maternal multivitamin use and smoking, and the risk of spina bifida
The NAT1 C1095A polymorphism, maternal multivitamin use and smoking, and the risk of spina bifida
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DOI：
10.1002/bdra.20143
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发表时间：
2005-07-01
影响因子：
--
通讯作者：
Mitchell, LE
中科院分区：
文献类型：
--
作者：
Jensen, LE;Hoess, K;Mitchell, LE
背景：产妇妊娠期补充叶酸可降低新生儿神经管缺陷（NTD）的风险，但其潜在的叶酸依赖性保护机制尚不清楚。n -乙酰转移酶1参与芳香胺和杂环胺的乙酰化以及叶酸的分解代谢。因此，编码n -乙酰转移酶1的基因NAT1的功能多态性可能是NTDs的危险因素。这些变异可能通过其在乙酰化或叶酸分解代谢中的作用对NTDs的风险产生影响，并可能通过母体或胚胎基因型起作用。方法：获得NAT1 C1095A基因型和孕产妇、围孕期多种维生素使用和吸烟信息，作为脊柱裂家庭研究的一部分。使用对数线性模型评估脊柱裂与胚胎和母体NAT1 C1095A基因型之间的关系，以及潜在的NAT1 C1095A基因型与暴露的相互作用。结果：分析没有提供证据表明胚胎或母体NAT1 C1095基因型独立影响脊柱裂的风险，或通过与母体使用多种维生素的相互作用。有证据表明，胚胎NAT1 C1095A基因型，可能还有母体NAT1 C1095A基因型，通过与母体吸烟状况的相互作用影响脊柱裂的风险。结论：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，这些分析的结果提供了初步证据，表明这种多态性可能与怀孕早期吸烟妇女的后代脊柱裂的风险有关。
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.