Kaare M, Ulander V-M, Painter J N, Ahvenainen T, Kaaja R, Aittomäki K
Folkhälsan Institute of Genetics, University of Helsinki, Finland.
Hum Reprod. 2007 Mar;22(3):864-8. doi: 10.1093/humrep/del436. Epub 2006 Nov 11.
Recurrent miscarriage (RM) has been suggested to be caused by mutations in genes coding for various coagulation factors resulting in thrombophilia. Mouse models indicate that genes involved in the protein C anticoagulant pathway are essential for normal embryonic development. Loss of function of two of these genes, thrombomodulin (TM) and endothelial protein C receptor (EPCR), causes embryonic lethality in mice. The aim of this study was to determine whether variations in the human TM or EPCR genes are associated with an increased risk for RM.
Forty-six RM patients and 191 controls were screened for mutations in TM and EPCR using denaturing high-performance liquid chromatography (DHPLC). The partners of 40 RM patients were also screened.
One exonic and one intronic variation in TM and two exonic and two intronic sequences in EPCR were detected. Four variants were common in both patients and controls. A previously identified truncating mutation in EPCR, suggested to have a role in pregnancy complications, was identified in two patients and one control. A novel deletion in the 3'UTR region of TM was detected, but its significance remains unsolved.
These data suggest that mutations in the TM or EPCR genes are not a major cause of RM, although they may exert a modifier effect in combination with other variants.
复发性流产（RM）被认为是由编码各种凝血因子的基因突变导致血栓形成倾向引起的。小鼠模型表明，参与蛋白C抗凝途径的基因对正常胚胎发育至关重要。其中两个基因，血栓调节蛋白（TM）和内皮蛋白C受体（EPCR）功能丧失会导致小鼠胚胎致死。本研究的目的是确定人类TM或EPCR基因的变异是否与RM风险增加相关。
采用变性高效液相色谱（DHPLC）对46例RM患者和191例对照进行TM和EPCR基因突变筛查。还对40例RM患者的配偶进行了筛查。
在TM中检测到1个外显子变异和1个内含子变异，在EPCR中检测到2个外显子和2个内含子序列变异。4个变异在患者和对照中均常见。在2例患者和1例对照中发现了先前确定的EPCR截短突变，该突变被认为与妊娠并发症有关。在TM的3'UTR区域检测到一个新的缺失，但其意义尚不清楚。
这些数据表明，TM或EPCR基因的突变不是RM的主要原因，尽管它们可能与其他变异共同发挥修饰作用。
