Bezerra J F, Oliveira G H M, Soares C D, Cardoso M L, Ururahy M A G, Neto F P F, Lima-Neto L G, Luchessi A D, Silbiger V N, Fajardo C M, Oliveira S R de, Almeida M das G, Hirata R D C, Rezende A A de, Hirata M H
Department of Clinical and Toxicological Analysis, Federal University of Rio Grande do Norte, Natal, RN, Brazil.
Oral Dis. 2015 Apr;21(3):393-9. doi: 10.1111/odi.12292. Epub 2014 Oct 8.
We investigated the relationship between non-syndromic cleft lip/palate (NSCLP) and polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR), and RFC1, as well as the corresponding interactions with environmental factors.
One hundred and forty NSCLP patients and their mothers, as well as 175 control individuals and their mothers, were recruited. Information regarding smoking and alcohol consumption was recorded. Blood samples were obtained in order to measure serum folate and cobalamin, as well as, plasma total homocysteine concentrations and to extract DNA. Polymorphisms in MTHFR(677C>T and 1298A>C), MTR(2756A>G), MTR(66A>G), and RFC1(80A>G) were analyzed by PCR-restriction fragment length polymorphism.
Among the patients, 59.5% had cleft lip and palate, 22.0% had cleft palate, and 18.5% had cleft lip only. Maternal alcohol consumption and reduced folic acid concentrations in both children and mothers (P < 0.001 and P = 0.003, respectively) were risk factors for NSCLP. Patients and their mothers carrying the MTHFR 667T allele showed lower serum folate than CC (P = 0.011 and P = 0.030, respectively). Mothers who carried the MTHFR 1298C allele exhibited increased risk of having a child with NSCLP, after adjusting for alcohol consumption (OR: 1.75, 95% CI: 1.03-2.99, P = 0.038).
Reduced folic acid levels, alcohol consumption, and the MTHFR 677T and 1298C alleles may have contributed to NSCLP development in this sample population from Rio Grande do Norte.
我们研究了非综合征性唇腭裂（NSCLP）与亚甲基四氢叶酸还原酶（MTHFR）、甲硫氨酸合成酶（MTR）、甲硫氨酸合成酶还原酶（MTRR）和还原型叶酸载体1（RFC1）基因多态性之间的关系，以及它们与环境因素的相应相互作用。
招募了140例NSCLP患者及其母亲，以及175名对照个体及其母亲。记录了吸烟和饮酒信息。采集血样以测量血清叶酸和钴胺素，以及血浆总同型半胱氨酸浓度，并提取DNA。通过聚合酶链反应-限制性片段长度多态性分析MTHFR（677C>T和1298A>C）、MTR（2756A>G）、MTR（66A>G）和RFC1（80A>G）基因的多态性。
在患者中，59.5%患有唇腭裂，22.0%患有腭裂，18.5%仅患有唇裂。母亲饮酒以及儿童和母亲体内叶酸浓度降低（分别为P<0.001和P=0.003）是NSCLP的危险因素。携带MTHFR 667T等位基因的患者及其母亲血清叶酸水平低于CC基因型者（分别为P=0.011和P=0.030）。在调整饮酒因素后，携带MTHFR 1298C等位基因的母亲生育NSCLP患儿的风险增加（比值比：1.75，95%可信区间：1.03-2.99，P=0.038）。
叶酸水平降低、饮酒以及MTHFR 677T和1298C等位基因可能促成了北里奥格兰德州该样本人群中NSCLP的发生。
