Lammer Edward J, Shaw Gary M, Iovannisci David M, Finnell Richard H
Children's Hospital Research Institute, Oakland, California 94609, USA.
Birth Defects Res A Clin Mol Teratol. 2004 Nov;70(11):846-52. doi: 10.1002/bdra.20081.
Periconceptional supplementation of multivitamins that include folic acid have been shown to prevent several birth defects, including neural tube defects and orofacial clefts. We investigated whether polymorphic variants of fetal acetyl-N-transferase 1 (NAT1), an enzyme involved in the catabolism of folates, differentially interacted with maternal multivitamin use during early pregnancy to alter the risk of delivering an infant with an orofacial cleft malformation.
Using a large population-based case-control study, we genotyped 421 California infants born with an isolated cleft and 299 controls for two NAT1 polymorphisms.
Compared to the homozygous wild-type genotypes, odds ratios for isolated cleft lip with/without cleft palate were slightly increased among infants who were homozygous for the variant alleles of NAT1 1088 and 1095. For isolated cleft palate, no similar associations with these two NAT1 variants were observed. For NAT1 1088 genotypes, we did not observe any differential risks for clefts related to maternal multivitamin intake. For NAT1 1095 genotypes, however, we found a two-fold higher risk for isolated cleft lip with/without cleft palate among infants who were homozygous for the variant allele and whose mothers did not take multivitamins during early pregnancy.
We found evidence suggestive of an interaction between the NAT1 1095 polymorphism and lack of maternal multivitamin use that increased risks of isolated cleft lip with/without cleft palate.
围孕期补充包含叶酸的多种维生素已被证明可预防多种出生缺陷，包括神经管缺陷和口面部裂隙。我们调查了胎儿乙酰 - N - 转移酶1（NAT1）的多态性变体（一种参与叶酸分解代谢的酶）是否在孕早期与母亲使用多种维生素存在差异相互作用，从而改变生出患有口面部裂隙畸形婴儿的风险。
利用一项基于人群的大型病例对照研究，我们对421名患有孤立性裂隙的加利福尼亚婴儿和299名对照进行了两种NAT1多态性的基因分型。
与纯合野生型基因型相比，NAT1 1088和1095变体等位基因纯合的婴儿中，孤立性唇裂伴或不伴腭裂的比值比略有增加。对于孤立性腭裂，未观察到与这两种NAT1变体有类似关联。对于NAT1 1088基因型，我们未观察到与母亲多种维生素摄入相关的腭裂差异风险。然而，对于NAT1 1095基因型，我们发现变体等位基因纯合且母亲在孕早期未服用多种维生素的婴儿中，孤立性唇裂伴或不伴腭裂的风险高出两倍。
我们发现有证据表明NAT1 1095多态性与母亲未使用多种维生素之间存在相互作用，这增加了孤立性唇裂伴或不伴腭裂的风险。
