Biguzzi E, Franchi F, Acaia B, Ossola W, Nava U, Paraboschi E M, Asselta R, Peyvandi F
Angelo Bianchi Bonomi Haemophilia and Thrombosis Center, IRCCS Fondazione Cà Granda Policlinico, University of Milan, Milan, Italy.
Haemophilia. 2014 Nov;20(6):e377-83. doi: 10.1111/hae.12514. Epub 2014 Oct 21.
Postpartum haemorrhage (PPH) is a leading cause of maternal mortality, particularly in the developing countries, and of severe maternal morbidity worldwide. To investigate the impact of genetic influences on postpartum haemorrhage, in association with maternal and intrapartum risk factors, using a candidate gene approach. All women (n = 6694) who underwent a vaginal delivery at the Obstetric Unit of a large University hospital in Milan (Italy) between July 2007 and September 2009 were enrolled. The first consecutive 3219 women entered the genetic study. Postpartum haemorrhage was defined as ≥500 mL blood loss. Eight functional polymorphisms in seven candidate genes were chosen because of their potential role in predisposing to or protecting from haemorrhagic conditions: tissue factor (F3), factor V (F5), tissue factor pathway inhibitor (TFPI), platelet glycoprotein Ia/IIa (ITGA2), prothrombin (F2), platelet glycoproteins Ibα (GP1BA) and angiotensin-converting enzyme (ACE). After correction for the already known PPH risk factors, only the promoter polymorphism of the tissue factor gene (F3 -603A>G) showed a significant association with PPH, the G allele exerting a protective effect (P = 0.00053; OR = 0.79, 95% CI = 0.69-0.90). The protective effect against PPH of the TF -603A>G polymorphism is biologically plausible since the G allele is associated with an increased protein expression and Tissue Factor is strongly represented in the placenta at term, particularly in decidual cells of maternal origin.
产后出血（PPH）是孕产妇死亡的主要原因，在发展中国家尤为如此，也是全球严重孕产妇发病的原因。为了研究基因影响与孕产妇和分娩期风险因素相关联时对产后出血的影响，采用候选基因方法。纳入了2007年7月至2009年9月期间在意大利米兰一家大型大学医院产科进行阴道分娩的所有妇女（n = 6694）。最初连续的3219名妇女进入基因研究。产后出血定义为失血量≥500 mL。选择了七个候选基因中的八个功能多态性，因为它们在易患或预防出血性疾病方面具有潜在作用：组织因子（F3）、因子V（F5）、组织因子途径抑制剂（TFPI）、血小板糖蛋白Ia/IIa（ITGA2）、凝血酶原（F2）、血小板糖蛋白Ibα（GP1BA）和血管紧张素转换酶（ACE）。在校正已知的产后出血风险因素后，只有组织因子基因的启动子多态性（F3 -603A>G）与产后出血有显著关联，G等位基因发挥保护作用（P = 0.00053；OR = 0.79，95%CI = 0.69-0.90）。TF -603A>G多态性对产后出血的保护作用在生物学上是合理的，因为G等位基因与蛋白质表达增加相关，并且足月时组织因子在胎盘中大量表达，特别是在母体来源的蜕膜细胞中。
