原因不明复发性流产患者血中亚甲基四氢叶酸还原酶基因C677T和A1298C位点突变的研究

C677T and A1298C mutation of the methylenetetrahydrofolate reductase gene in unexplained recurrent spontaneous abortion

目的 探讨 5 ,10 亚甲基四氢叶酸还原酶基因C6 77T和A12 98C位点突变与原因不明复发性流产 (unexplainedrecurrentspontaneousabortion ,URSA)易感因素的相关性。 方法 采用PCR-限制性片段长度多态性方法 ,检测 14 7例原因不明复发性流产患者 (URSA组 )和 82例有正常妊娠史的妇女 (对照组 )血中亚甲基四氢叶酸还原酶基因C6 77T和A12 98C位点突变。结果 ( 1)C6 77T的 3种基因型在URSA组和对照组总体分布存在显著性差异 (P =0 0 12 ) ,其中URSA组 :基因型CC占 33 3% ,CT占 5 3 1% ,TT占 13 6 % ,对照组 :基因型CC占 5 2 4 % ,CT占 5 1 5 % ,TT占 6 1%。两组 6 77CC基因表达差异有显著性 (P =0 0 0 5 ) ,URSA组C和T等位基因分别为 4 0 1%、5 9 9% ,两组基因分布情况比较 ,差异有显著性 (P <0 0 0 5 ) ;( 2 )A12 98C的 3种基因型在URSA组和对照组中总体分布情况比较 ,差异无显著性 ,12 98AA/AC/CC基因型和A/C等位基因频率比较 ,差异无显著性 (P >0 0 0 5 ) ;( 3)C6 77T/A12 98C连锁基因分析显示 ,8种连锁基因型中 ,URSA组 6 77CC/ 12 98AA表达频率显著降低 ,而 6 77(CT +TT) / 12 98CC仅在URSA组中表达。结论 URSA与亚甲基四氢叶酸还原酶基因C6 77T和A12 98C位点突变有关。

Objective To investigate the association between the C677T and A1298C mutation of 5,10 methylenetetrahydrofolate reductase(MTHFR) gene and unexplained recurrent spontaneous abortion(URSA) in Chinese population Methods Polymerase chain reaction restriction fragment length polymorphism(PCR RFLP) was used to detect the mutation of C677T and A1298C of MTHFR in 148 cases with URSA and 82 normal controls Results (1) The distribution frequencies of C667T associated 3 genotypes between the URSA and control group showed statistically significant difference ( P =0 012) The frequencies of C677T genotypes were : CC(33 3%),CT(53 1%) ,TT(13 6%) in URSA group and CC(52 4%),CT(51 5%), TT(6 1%) in control group , respectively And the frequency of CC genotype in URSA group was decreased significantly( P =0 005), while the frequency of T allele in URSA was increased( P <0 005) (2) The prevalence of the MTHFR A1298C associated 3 genotypes and A/C alleles in URSA group did not differ significantly from the control (3) According to the linkage analysis of C677T and A1298C, 8 linkage genotypes were found, and the frequency of 677CC/1298AA in URSA was significantly lower compared with the control, the linkage of 677(CT+TT)/1298CC was only observed in URSA group Conclusions The mutations of MTHFR C677T and A1298C play a role in the mechanism of unexplained recurrent spontaneous abortion