红细胞叶酸水平及叶酸代谢相关基因多态性与不良妊娠结局的相关性研究  

Study on the relationship of erythrocyte folate status,polymorphic variation in folate-related genes and adverse pregnancy outcomes

作　　者：王涛[1] 高劲松[1] 边旭明[1] 孙念怙[1] 刘俊涛[1] 刘欣燕[1] 

机构地区：[1]中国医学科学院北京协和医学院北京协和医院妇产科,北京100730

出　　处：《生殖医学杂志》2010年第1期48-52,共5页Journal of Reproductive Medicine

摘　　要：目的检测不良妊娠结局患者叶酸水平及叶酸代谢相关基因亚甲基四氢叶酸还原酶(MTHFR)677C>T、1298A>C、还原叶酸载体(RFC-1)80A>G的基因多态性分布,探讨其与不良妊娠结局的相关性。方法选取北京协和医院不良妊娠结局患者63例,正常对照人群48例,检测血清叶酸、红细胞叶酸和维生素B_(12);运用聚合酶链反应-限制性内切酶酶切片断长度多态性(PCR-RFLP)的方法检测相关基因MTHFR 677C>T、1298A>C、RFC-1 80A>G的基因多态性;比较病例组和对照组叶酸水平和基因型分布的差异,以及不同基因型叶酸水平的差异。结果病例组虽然血清叶酸水平高于对照组,但红细胞叶酸水平显著低于对照组,分别为(234±1 20)μg/L和(284±88)μg/L(P<0.05)。MTHFR 677CT与677CC在对照组和病例组之间的分布具有显著性差异(P<0.05)。RFC-1 80GG与80AA在对照组和病例组之间的分布有显著性差异(P<0.05)。RFC-1 80GG组对叶酸的转运(红细胞/血清叶酸比值)下降,与80AA组相比具有显著差异(P<0.05)。结论红细胞叶酸水平降低与不良妊娠结局相关,MTHFR 677C>T和RFC-1 80A>G突变可能是发生不良妊娠结局的高危因素。Objective： To investigate the relationship among folic acid status, folate metabolism-related gene polymorphisms and the adverse pregnancy outcomes. Methods： A case-control study was carried out in Peking Union Medical College Hospital. Serum folic acid and erythrocyte folic acid levels were measured in 63 women with adverse pregnancy outcomes and 48 normal controls, and compared between the two groups. Polymorphisms in methylene-tetrahydrofolate reductase（MTHFR 677C〉T, 1298A〉C） and the reduced folate carrier（RFC1 80G〉A） were determined by PCR-RFLP method and compared between the two groups. The relationship between folate metabolism-related gene polymorphisms and folic acid levels was also studied. Results： The erythrocyte folic acid levels were significantly pregnancy outcomes than in normal controls（234~ 120 μg/L vs. 28 genotypes were shown to be in Hardy-Weinberg equilibrium. The 677CC was significantly different between the two groups （P MTHFR, 1298A〉C, was less frequently observed in both groups. lower in the women with adverse 4±88 μg/L, P〈0.05）. All studied distribution of MTHFR 677CT and 0.05）. A second The distribution of polymorphism in RFC-1 80GG and AA was significantly different between the two groups （P〈0. 05）. The RFC-1 80GG subgroup had a significantly lower erythrocyte/serum folic acid ratio compared with 80AA subgroup （P 〈 0.05）,suggesting impaired transportation of folic acid in RFC-1 80GG subgroup. Conclusions： Low erythrocyte folic acid level is likely to be related with adverse pregnancy outcomes. MTHFR 677C〉T and RFC-1 80A〉G polymorphisms may contribute to adverse pregnancy outcomes. MTHFR 1298A〉C was less frequently observed in both cases and controls. RFC-1 80A〉G polymorphism may be responsible for the decreasing of erythrocyte folic acid level.

关 键 词：亚甲基四氢叶酸还原酶 基因多态性 妊娠结局 红细胞 MTHFR基因 作者 酸相 HARDY 

分 类 号：Q987[生物学—遗传学] Q346.5[生物学—人类学]