作　　者： ; ; ; ; ;

机构地区： 蚌埠医学院

出　　处： 《遗传》 2010年第5期461-466,共6页

摘　　要： 为探讨年轻母亲叶酸代谢相关基因MTHFR677C>T、MTRR66A>G、RFC-180G>A和MTR2756A>G多态性与唐氏综合征(Down syndrome,DS)发生的关系,采用随机病例-对照研究设计,应用PCR-RFLP方法检测60例DS患儿的母亲与68例正常生育女性的基因型。经χ2检验,MTHFR基因T等位基因频率在病例组和对照组中差异有统计学意义(P<0.05),而MTRR、MTR和RFC-1等位基因频率差异无统计学意义。Logistic回归分析显示:携带MTHFRTT基因型的母亲孕育DS患儿的风险显著增加(OR=3.51,95%CI=1.30～9.46,P<0.05),而杂合子CT以及CT合并TT基因型与DS发生风险无显著关联;携带MTRRGG基因型的母亲孕育DS患儿的风险增加3.16倍(OR=3.16,95%CI=1.20～8.35,P<0.05),而RFC-1和MTR突变基因型与DS发生风险无显著关联;MTHFR(CT+TT)/MTRR GG、MTHFR(CT+TT)/RFC-1 AA、MTHFR CC/MTR(AG+GG)、MTHFR(CT+TT)/MTR AA、MTRRGG/MTR AA和RFC-1 AA/MTR AA联合基因型与DS发生风险显著相关。结果表明,年轻女性MTHFR 677C>T、MTRR 66A>G位点变异是孕育DS患儿的独立风险因子,尚不能认为RFC-1 80G>A、MTR 2756A>G多态性与DS发生相关,而基因与基因多态位点之间存在交互和修饰效应。 To explore the relationship between genetic polymorphisms in methylenetetrahydrofolate reductase（MTHFR）,methionine synthase reductase（MTRR）,reduced folate carrier1（RFC-1）,methionine synthase（MTR） involved in folate metabolism and the risk of offsprings of young Chinese women with Down syndrome（DS） through a case-control study,the polymorphisms of MTHFR 677CT,MTRR 66AG,RFC-1 80GA,and MTR 2756AG in 60 mothers of children with DS and 68 control mothers were investigated by PCR-RFLP.Significant differences in allelic frequencies were present between the cases and controls for MTHFR（P0.05）,but not in allelic frequencies for MTRR,RFC-1,and MTR.Homozygous MTHFR 677CT polymorphism was more prevalent among the mothers of children with DS than among the control mothers,with an odds ratio of 3.51（OR=3.51,95% CI=1.30～9.46,P0.05）.No significant association was observed in the combined heterozygotes.In addition,the homozygous MTRR 66AG polymorphism was independently associated with a 3.16-fold increase in estimated risk（OR=3.16,95% CI=1.20～8.35,P0.05）.The increased risk of DS for homozygous RFC-1 80GA was not associated with MTR 2756AG.Positive interactions were found for the following genotype-pairs：MTHFR（CT＋TT）/MTRR GG,MTHFR（CT＋TT）/RFC-1 AA,MTHFR CC/MTR（AG＋GG）,MTHFR（CT＋TT）/MTR AA,MTRR GG/MTR AA,and RFC-1 AA/MTRAA.In conclusion,MTHFR 677CT and MTRR 66AG polymorphisms are two independent risk factors for DS pregnancies in young women,but RFC-1 80GA and MTR 2756AG polymorphism are not independent risk factor.A role for combined genotypes in the risk of DS pregnancies cannot be excluded.

关 键 词： 唐氏综合征 亚甲基四氢叶酸还原酶 甲硫氨酸合成还原酶 还原叶酸载体基因 蛋氨酸合酶 多态性

领　　域： [生物学]