原因不明复发性流产遗传性血凝因素研究

目的研究凝血因子V基因G1691A、凝血酶原基因G20210A以及5,10-亚甲基四氢叶酸还原酶(MTHFR)基因C677T和A1298C位点突变,与原因不明复发性流产易感相关性。方法采用聚合酶链式反应-限制性片断长度多态性分析方法,检测148例原因不明复发性流产者和82例正常对照的凝血因子V基因G1691A、凝血酶原G20210A以及MTHFR基因C677T和A1298C位点突变情况。结果复发性流产组和对照组,均未发现凝血因子V基因G1691A和凝血酶原基因G20210A突变;MTHFR基因C667T三种基因型在两组的总体分布存在显著性差异(P=0.012),其中复发性流产组CC基因型表达频率显著降低(P=0.005),T等位基因表达频率显著增大(P=0.004);MTHFR基因A1298C三种基因型在复发性流产和对照组总体分布无显著差异,AA/AC/CC基因型和A/C等位基因频率表达无统计学差异;MTHFR基因C677T/A1298C连锁分析发现8种连锁基因型,复发性流产组中677CC/1298AA表达频率显著降低(P<0.05),而677(CT TT)/1298CC仅在复发性流产组中表达(P<0.05)。结论中国人群复发性流产与凝血因子V基因G1691A和凝血酶原G20210A基因突变无关,而与MTHFR基因C677T和A1298C位点突变有关。

Inherited Thrombophilia Factors in Patients with Unexplained Recurrent Spontaneous Abortion

Objective To investigate the mutation of Factor V G1691A,prothrombin G20210A,5,10-methylenetetrahydrofolate reductase(MTHFR) C677T and A1298C in patients with unexplained recurrent spontaneous abortion(RSA) in Chinese population. Methods Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) was employed to detect the mutation of Factor V G1691A, prothrombin G20210A,MTHFR C677T and A1298C of MTHFR in 148 patients with RSA and 82 normal controls. Results No mutation of Factor V G1691A and prothrombin G20210A was observed in the patients.The frequencies of the three C667T associated genotypes distributed between RSA and control group reached the statistical significance as a whole(P=0.012).The frequency of genotype CC was significantly decreased(P=0.005),and allele T was significantly increased(P=(0.004)) in RSA group.The prevalence of MTHFR A1298C associated genotypes,1298AA/AC/CC,and A/C alleles in RSA cases do not differ significantly from the controls.According to the linkage of C677T and A1298C,8 linkaged genotypes were found,and the frequency of 677CC/1298AA in RSA was decreased significantly compared with the controls(P<0.05),and the linkage of 677(CT TT)/1298CC was only observed in RSA group with statistical(significance)(P<0.05). Conclusion The mutations of Factor V G1691A and prothrombin G20210A are not asso-(ciated) with the susceptibility to RSA,however,the mutations of MTHFR C677T and A1298C play a role in the(mechanism) of RSA in Chinese population.