孕母高剂量叶酸摄入与MTHFR基因C677T多态性对子代单纯性尿道下裂的发病风险研究

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目的探讨高剂量叶酸摄入与亚甲基四氢叶酸还原酶(methylenetrahydrofolate reductase,MTHFR)基因多态性间交互作用对子代单纯性尿道下裂(Isolated Hypospadias,IH)发病的影响。方法通过病例对照研究回顾性分析温州地区近5年来分娩的80例单纯性尿道下裂患儿和同期分娩的120例正常儿(对照组)的孕母环境及遗传高危因素,根据孕母不良孕产史、家族史以及叶酸摄入情况,将病例组分成A、B两组,将对照组分成C、D两组。进一步应用焦磷酸测序检测MTHFR基因C677T多态性,并分析其与叶酸摄入的交互作用。结果病例组孕母大剂量叶酸摄入者17例(占21.3%),对照组78例(占65%),两者差异有统计学意义,孕母大剂量叶酸摄入者子代重型IH患者0例,而叶酸摄入不足者子代重型IH患者10例,两者差异有统计学意义。将4组病例进行孕母MTHFR C677T基因多态性检测,发现A、B、C组TT基因型比例显著高于D组,且等位基因T差异也有显著性。结论孕母MTHFR C677T基因多态性合并叶酸补充不足可能增加子代IH发病风险。孕前及孕早期孕母大剂量叶酸摄入可能对子代IH的发病具有保护作用或使子代IH发病的严重程度下降。 Objective To investigate the effect of high dose folic acid intake and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism on the pathogenesis of isolated hypospadias (IH). Methods A case-control study was conducted to retrospectively analyze the maternal environmental and genetic risk factors of 80 cases of simple hypospadias and 120 cases of normal children (control group) who gave birth in the past five years in Wenzhou. Birth history, family history and the intake of folic acid. The cases were divided into A and B groups, and the control group was divided into C and D groups. Pyrosequencing was further used to detect MTHFR gene C677T polymorphism and its interaction with folic acid intake was analyzed. Results In the case group, 17 cases (21.3%) were pregnant with high-dose folate intake and 78 cases (65%) with control group. The difference was statistically significant. 0 cases, and folic acid intake in 10 cases of sub-generational IH patients, the difference was statistically significant. The polymorphism of MTHFR C677T gene in pregnant women was detected in four groups. The proportion of TT genotypes in groups A, B and C was significantly higher than that in group D, and the difference of allele T was also significant. Conclusion Pregnancy MTHFR C677T gene polymorphism combined with insufficient folic acid supplementation may increase the risk of developing IH. Pre-pregnancy and early pregnancy high-dose pregnant mother’s intake of folic acid may have protective effect on the incidence of IH or offspring to reduce the severity of IH offspring.
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