亲代MTHFR基因677C／T多态性与子代非综合征性唇腭裂的相关性

Association between parental MTHFR gene polymorphism 677C/T and nonsyndromic cleft lip and palate in offspring

目的探讨山东地区亲代亚甲基四氢叶酸还原酶（methylenetetrahydrofolate reductase，MTHFR）基因677C／T多态性与子代发生非综合征性唇腭裂（nonsyndromic cleft lip with or without cleft palate，NSCL／P）的关联。方法应用聚合酶链反应一限制性片段长度多态性分析技术（polymerasechainreaction—restrictionfragmentlengthpolymorphism，PCR-RFLP）对2006年8月至2008年8月在齐鲁医院治疗的89对NSCL／P患者亲代和64对健康查体儿童亲代的MTHFR基因677C／T多态性进行检测。结果患者母亲与正常儿童母亲的T等位基因频率分别为65．73％和46．09％，C等位基因频率分别为34．27％和53．91％，其构成比差异有统计学意义（x2=13．663，P〈O．01）；携带T等位基因的母亲子代患NSCL／P的风险为未携带T等位基因的母亲子代的2．243倍（95％CI：1．408~3．572）。患者的父亲与正常儿童父亲的T等位基因频率分别为62．92％和55．47％；C等位基因频率分别为37．08％和44．53％，其构成比差异无统计学意义（Y。=2．222，P〉0．05）；病例组和对照组后代可能为纯合突变胎儿的机率分别为43％和29％（P〉0．05）。结论山东地区母亲的MTHFR基因677C／T突变对后代NSCL／P的发生有重要的影响；父亲的MTHFR基因677C／T突变则可能不是子代患NSCL／P的风险因素。

Objective To explore the association between parental genetic polymorphism of metbylenetetrahydrofolate reductase （MTHFR） 677C/T and occurrence of nonsyndromic cleft lip with or without cleft palate （NSCL/P） in offspring in Shandong Province. Methods MTHFR genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）. Parents of 89 NSCL/P patients treated at Qilu Hospital from August, 2006 to August, 2008 and those of 64 healthy children were recruited in this ease-control study. Results Frequencies of T and C alleles in mothers of patients and healthy children were 65.73% and 46.09%, and 34.27% and 53.91%, respectively （x2 = 13. 663, P〈0.01）. Offspring whose mothers had T alleles were 2. 243 times more likely to develop NSCL/ P （95%CI： 1. 408-3. 572）. Frequencies of T and C alleles in fathers of patients and healthy children were 62.92% and 55.47%, and 37.08% and 44.53%, respectively （2：2.222, P〉0.05）. The chance for parents of the patient and control groups to bear an affected fetus carrying homozygous mutations were 43% and 29%, respectively （P〉0.05）. Conclusion In Shandong Province, maternal genotype for the MTHFR 677C/T polymorphism has a significant impact on the occurrence of NSCL/P in their offspring, whilst paternal genotype for this polymorphism may not be a risk factor for NSCL/P in their offspring.