Division of Genetics, Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, 138 Sheng-Li Road, Tainan, 704 Taiwan.
Thromb Haemost. 2013 Jan;109(1):8-15. doi: 10.1160/TH12-08-0584. Epub 2012 Nov 22.
A fine balance between coagulation and fibrinolysis is critical in early pregnancy. Plasminogen activator inhibitor-1 (PAI-1) and angiotensin converting enzyme (ACE) are involved in the fibrinolytic process, and several studies have reported the association between their gene polymorphisms and recurrent pregnancy loss (RPL). This study was conducted to investigate the association between PAI-1 and ACE polymorphisms and idiopathic RPL, using meta-analyses. A systematic review of the published literature from the MEDLINE and EMBASE databases before April 2012 was conducted. Of 209 potentially relevant studies, 22 case-control studies comprising a total of 2,820 RPL patients and 3,009 controls were included. Among these studies were 11 reports of PAI-1 4G/5G and 11 of ACE I/D polymorphisms in patients with RPL. A significant association was found withthe ACE I/D polymorphism [summary odds ratio 1.29 (95% confidence interval 1.02-1.62)] in studies including more than two recurrent abortions. Subgroup analysis did not show significant associations with RPL in Caucasian and non-Caucasian patients. Meta-analyses of PAI-1 4G/5G polymorphism were not found associations with RPL in studies including more than two or three recurrent abortions, and in studies of Caucasian and non-Caucasian patients. In conclusion, meta-analyses showed a significant association between the ACE I/D polymorphism and idiopathic RPL. High clinical heterogeneity existed among studies of PAI-1 4G/5G, and the aggregated data failed to confer higher susceptibility to idiopathic RPL. More well-designed studies with different ethnic populations are required for future integration.
在早期妊娠中，凝血和纤维蛋白溶解之间的平衡至关重要。纤溶酶原激活物抑制剂-1（PAI-1）和血管紧张素转换酶（ACE）参与纤维蛋白溶解过程，多项研究报道了它们的基因多态性与复发性妊娠丢失（RPL）之间的关联。本研究采用荟萃分析来探讨 PAI-1 和 ACE 多态性与特发性 RPL 之间的关联。对 2012 年 4 月前 MEDLINE 和 EMBASE 数据库中已发表的文献进行了系统回顾。在 209 项可能相关的研究中，有 22 项病例对照研究共纳入 2820 例 RPL 患者和 3009 例对照。其中 11 项研究报道了 PAI-1 4G/5G 多态性，11 项研究报道了 ACE I/D 多态性。在包括两次以上习惯性流产的研究中，ACE I/D 多态性存在显著相关性[汇总优势比 1.29（95%置信区间 1.02-1.62）]。亚组分析显示，在白种人和非白种人患者中，与 RPL 无显著相关性。荟萃分析显示，在包括两次或三次以上习惯性流产的研究中，以及在白种人和非白种人患者的研究中，PAI-1 4G/5G 多态性与 RPL 无相关性。总之，荟萃分析显示 ACE I/D 多态性与特发性 RPL 之间存在显著相关性。PAI-1 4G/5G 的研究存在较高的临床异质性，汇总数据未能显示其对特发性 RPL 的更高易感性。需要进一步开展不同种族人群的设计良好的研究来进行综合分析。
