No major role for periconceptional folic acid use and its interaction with the MTHFR C677T polymorphism in the etiology of congenital anorectal malformations.
No major role for periconceptional folic acid use and its interaction with the MTHFR C677T polymorphism in the etiology of congenital anorectal malformations.
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DOI：
10.1002/bdra.23256
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发表时间：
2014-06
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影响因子：
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通讯作者：
C. Wijers;I. de Blaauw;N. Zwink;Markus Draaken;Loes F. M. van der Zanden;H. Brunner;A. Brooks;R. Hofstra;C. Sloots;P. Broens;M. Wijnen;M. Ludwig;E. Jenetzky;H. Reutter;C. Marcelis;N. Roeleveld;I. V. van Rooij
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作者：
C. Wijers;I. de Blaauw;N. Zwink;Markus Draaken;Loes F. M. van der Zanden;H. Brunner;A. Brooks;R. Hofstra;C. Sloots;P. Broens;M. Wijnen;M. Ludwig;E. Jenetzky;H. Reutter;C. Marcelis;N. Roeleveld;I. V. van Rooij
遗传和非遗传因素都被认为是先天性肛肠畸形（ARM）的病因。孕妇围孕期使用叶酸补充剂被不一致地建议在预防ARM中发挥作用。因此，我们研究了母亲孕产期叶酸补充剂的使用以及婴儿和母亲MTHFR（亚甲基四氢叶酸还原酶）C677T多态性与ARM和ARM亚群风险的独立关联和相互作用。方法对1990年至2012年出生的371例非综合征性ARM病例和714例人群对照进行病例-对照研究，采用母亲问卷和母婴DNA样本。病例在Radboud大学医学中心、Sophia儿童医院- erasmus MC鹿特丹、荷兰格罗宁根大学医学中心和德国各地的医院的儿科外科接受了ARM治疗。结果：在ARM组中，与叶酸的使用没有关联（优势比= 1.1；95%可信区间：0.8-1.4）。婴儿和母亲的MTHFR C677T多态性与分离的ARM尤其弱相关。缺乏叶酸补充剂与携带MTHFR C677T多态性的婴儿或母亲联合使用似乎不会增加ARM或ARM亚组的风险。由于相互作用而产生的相对超额风险在加性尺度上也没有明确表明相互作用。结论：这项研究首次调查了孕产期叶酸补充剂使用与婴儿和母亲MTHFR C677T多态性在ARM病因学中的相互作用，并没有提供这种基因-环境相互作用的证据。
BACKGROUND Both genetic and nongenetic factors are suggested to be involved in the etiology of congenital anorectal malformations (ARM). Maternal periconceptional use of folic acid supplements were inconsistently suggested to play a role in the prevention of ARM. Therefore, we investigated independent associations and interactions of maternal periconceptional folic acid supplement use and the infant and maternal MTHFR (methylenetetrahydrofolate reductase) C677T polymorphisms with the risk of ARM and subgroups of ARM. METHODS A case-control study was conducted among 371 nonsyndromic ARM cases and 714 population-based controls born between 1990 and 2012 using maternal questionnaires and DNA samples from mother and child. Cases were treated for ARM at departments of Pediatric Surgery of the Radboud university medical center, Sophia Children's Hospital-Erasmus MC Rotterdam, and the University Medical Center Groningen in The Netherlands and hospitals throughout Germany. RESULTS No association with folic acid use was present (odds ratio = 1.1; 95% confidence interval: 0.8-1.4) for ARM as a group. Infant and maternal MTHFR C677T polymorphisms were weakly associated with isolated ARM in particular. Lack of folic acid supplement use in combination with infants or mothers carrying the MTHFR C677T polymorphism did not seem to increase the risk of ARM or subgroups of ARM. The relative excess risks due to interaction did not clearly indicate interaction on an additive scale either. CONCLUSION This first study investigating interactions between periconceptional folic acid supplement use and infant and maternal MTHFR C677T polymorphisms in the etiology of ARM did not provide evidence for a role of this gene-environment interaction.