原因不明复发性流产遗传性血凝因素研究

Inherited Thrombophilia Factors in Patients with Unexplained Recurrent Spontaneous Abortion

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。

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 associated with the susceptibility to RSA, however, the mutations of MTHFR C677T and A1298C play a role in the mechanism of RSA in Chinese population.