Fetal and maternal MTHFR C677T genotype, maternal folate intake and the risk of nonsyndromic oral clefts
Fetal and maternal MTHFR C677T genotype, maternal folate intake and the risk of nonsyndromic oral clefts
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DOI：
10.1002/ajmg.a.31462
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发表时间：
2007-02-01
影响因子：
2
通讯作者：
Cordier, Sylvaine
中科院分区：
文献类型：
--
作者：
Chevrier, Cecile;Perret, Claire;Cordier, Sylvaine
在许多人群中研究了母亲叶酸摄入量与非综合征性口裂风险之间的关系，但结果相互矛盾。亚甲基四氢叶酸还原酶基因(MTHFR)在叶酸代谢中起重要作用，包括C677T在内的几个基因多态性在欧洲人群中很常见。法国一项研究(1998-2001)的数据让我们调查了母亲膳食叶酸摄入量和MTHFR基因多态性的作用，以及它们对唇裂合并/不合并腭裂(CL/P)和单纯腭裂(CP)风险的影响。我们使用病例对照(164个CUP，76个CP：236个对照；其中148、59、168个分别具有可用的基因)和病例-父母(143个CL/P和56个CP家系)研究设计，并区分儿童的基因和母亲中介效应对风险的作用。本研究观察了母亲膳食叶酸摄入量对子代患病风险的有利影响(OR(OR)(314微克/(天)=0.64，0.4-1.1；对于CP，OR[230-314微克/天]=1.15，0.6-2.2，OR>；314微克/(天)=0.70，0.3-1.4)。在病例对照分析中，我们观察到与儿童的TT基因型相关的风险降低(ORCC=ref；对于CL/P，Ortt=0.54，0.3-1.1；对于CP，Ortt=0.33，0.1-1.0)；在病例-父母分析中，无论是胎儿还是母亲，这种基因型都没有统计学意义。在我们的对照组中，TT基因型的频率高于法国以前报道的频率，这可以部分解释在病例对照比较中观察到的风险降低。交互作用在统计学上没有显著意义。然而，分层病例-父母分析显示，根据叶酸摄入量，TT基因型的作用略有不同。适度的样本量限制了这项研究，尽管如此，它对饮食叶酸摄入量和MTHFR多态对口裂的可能影响提供了新的估计。(C)2007年Wiley-Liss，Inc.
The association between maternal folate intake and risk of nonsyndromic oral clefts has been studied among many populations with conflicting results. The methylenetetrahydrofolate reductase gene (MTHFR) plays a major role in folate metabolism, and several polymorphisms, including C677T, are common in European Populations. Data from a French study (1998-2001) let us investigate the roles of maternal dietary folate intake and the MTHFR polymorphism and their interaction on the risk of cleft lip with/without cleft palate (CL/P) and cleft palate only (CP). We used both case-control (164 CUP, 76 CP: 236 controls; 148, 59, 168 of whom, respectively, had an available genotype) and case-parent (143 CL/P and 56 CP families) study designs and distinguished the role of the child's genotype and maternally mediated effects on risks. This study observed a beneficial effect of mothers' dietary folate intake on their offspring's risk (odds ratio (OR)( 314 mu g/ (day) = 0.64, 0.4-1.1; for CP, OR[230-314 mu g/day] = 1.15, 0.6-2.2, OR > 314 mu g/day = 0.70, 0.3-1.4). We observed a reduced risk associated with the TT genotype of the child in the case-control analysis (ORCC = ref; for CL/P, ORTT = 0.54, 0.3-1.1; for CP, ORTT = 0.33, 0.1-1.0); this genotype, either fetal or maternal, was not statistically significant in the case-parent analysis. A frequency of TT genotype higher in our control group than previously reported in France can partly explain the risk reduction observed in case-control comparison. Interactions were not statistically significant. Stratified case-parent analysis showed, however, slight heterogeneity in the role of TT genotype according to folate intake. The modest sample size limits this study, which nonetheless provides new estimate of the possible impact of dietary folate intake and MTHFR polymorphism on oral clefts. (c) 2007 Wiley-Liss, Inc.