复发性流产与人类白细胞抗原DQB1基因多态性关系的研究

Association of soluble human leukocyte antigen DQB1 with recurrent spontaneous abortion

目的探讨复发性流产与人类白细胞抗原DQB1(HLA-DQB1)基因多态性的关系。方法应用PCR限制性片段长度多态性方法(PCR-RFLP),分析36例无不良妊娠史的正常妇女(对照组)和61例复发性流产患者[观察组,其中抗心磷脂抗体阳性31例,抗心磷脂抗体阴性30例;早期流产28例,晚期流产22例,早晚期流产(2次以上的流产分别发生在早期或晚期)11例]的DQB1基因型。结果(1)观察组0201等位基因频率为16·4%(20/122),明显高于对照组的8·3%(6/72),但两组比较,差异无统计学意义(P>0·05);观察组DQB1第57位非天门冬氨酸频率明显高于对照组,两组比较,差异有统计学意义(P<0·05);观察组中早期流产者0201等位基因频率为23·2%(13/56),明显高于晚期流产者的4·5%(2/44),两者比较,差异有统计学意义(P<0·05);晚期流产者0303等位基因频率为27·3%(12/44),明显高于早期流产者的7·1%(4/56),两者比较,差异也有统计学意义(P<0·05)。(2)观察组中抗心磷脂抗体阳性者0303等位基因频率为26%(16/62),明显高于抗心磷脂抗体阴性者的7%(4/60),两者比较,差异有统计学意义(P<0·05)。结论DQB1第57位非天门冬氨酸可能与复发性流产的发生有关,DQB1*0201等位基因可能与早期流产有关,DQB1*0303等位基因可能与晚期流产及抗心磷脂抗体阳性者的流产发生有关。

Objective To investigate the relationship between the recurrent spontaneous abortion and soluble human leukocyte antigen （HLA） DQB1 gene polymorphism . Methods Sixty one eases with recurrent spontaneous abortion were included in study group. Of them, 31 were anticardiolipin antibody （ACA） positive,while 30 were negative. Twenty eight cases were with early abortion, 22 were with late abortion, and 11 were with both early and late abortions. Thirty six women without abnormal pregnancy history were recruited as control group. HLA-DQB1 genotyping was carried out by polymerase chain reaction- restrictive fragment length polymorphism （PCR-RFLP）. Results The frequency of DQB1 ＊ 0201allele in the study group （ 16.4%, 20/122） was higher than that in the control group （ 8.3%, 6/72）, but the difference was not statistically significant （ P 〉 0.05 ）. The frequency of 57 site with non Asp in the study group was significantly higher than that in the control group （P 〈 0.05 ）. The frequencies of both DQB1 ＊ 0201 and ＊ 0303 were significantly different among early abortion, late abortion and both early and late abortion groups（ P 〈 0.05 and P 〈 0.05）. The frequency of DQB1 ＊ 0201 was significantly higher in the early abortion group than that in the late abortion group （ P 〈 0. 01 ）. The frequency of DQB1 ＊ 0303 was significantly increased in the late abortion group when compared to that in the early group（ P 〈0. 01 ）. The frequency of DQB1 ＊ 0303 was found to be significantly higher in patients with ACA positive than that in ACA negative group （ P 〈 0.05 ）. Conduslon The 57 site with non Asp may be a gene related to recurrent spontaneous abortions. DQB1 ＊ 0201 may be correlated to the early abortion, while DQB1 ＊ 0303 correlated to the late abortion and abortion with ACA positive.