Human Reproduction, Vol. 18, No. 11, 2473-2477,
November 2003
© 2003 European Society of Human Reproduction and Embryology
Polymorphisms in the ACE and PAI-1 genes are associated with recurrent spontaneous miscarriages
1 Department of Obstetrics and Gynecology, 2 Department of Clinical Chemistry and 3 Department of Haematology and Oncology, Großhadern Hospital, Ludwig-Maximilians-University, 81377 Munich, Germany
4 To whom correspondence should be addressed. e-mail: cthaler{at}helios.med.uni-muenchen.de
BACKGROUND: Successful pregnancies require fine tuning of fibrinolytic activities in order to secure fibrin polymerization and stabilization of the placental basal plate as well as to prevent excess fibrin deposition in placental vessels and intervillous spaces. Fibrinolysis is tightly regulated by plasminogen activator inhibitor-1 (PAI-1). Endothelial PAI-1 synthesis is induced by angiotensin II, which is generated by angiotensin I-converting enzyme (ACE). METHODS: We studied the ACE deletion (D)/insertion (I) polymorphism and the PAI-1 4G/5G polymorphism in women with recurrent spontaneous miscarriages (RM). Both polymorphisms have been shown to be associated with ACE and PAI-1 expression levels respectively. A study group of 184 patients with a history of two or more consecutive unexplained spontaneous miscarriages was compared with a control group of 127 patients with uneventful term deliveries and no history of miscarriages. RESULTS: Our findings show: (i) homozygosity for the D allele of the ACE gene, which results in elevated PAI-1 concentrations and hypofibrinolysis, is associated with an elevated risk of RM; (ii) the combination of the D/D genotype with two 4G alleles of the PAI-1 promoter, which further increases PAI-1 plasma levels, is significantly more frequent in RM patients compared with controls. CONCLUSIONS: Based on these results, we recommend the incorporation of these two polymorphisms into the spectrum of thrombophilic mutations which should be analysed in individuals with recurrent spontaneous miscarriages. Patients homozygous for both the ACE D and PAI-1 4G alleles may benefit from the application of low molecular weight heparin as early as possible in the pregnancy in order to prevent uteroplacental microthromboses.
Key words: angiotensin I-converting enzyme/fibrinolysis/plasminogen activator inhibitor-1/pregnancy loss/thrombophilic gene polymorphism
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Monien, O. Kadecki, S. Baumgarten, A. Salama, T. Dorner, and H. Kiesewetter Use of Heparin in Women With Early and Late Miscarriages With and Without Thrombophilia Clinical and Applied Thrombosis/Hemostasis, December 1, 2009; 15(6): 636 - 644. [Abstract] [PDF]
|
|
|
|
 |
|
 L. L Valdez-Velazquez, A. Quintero-Ramos, S. A Perez, F. Mendoza-Carrera, H. Montoya-Fuentes, F. Rivas Jr, N. Olivares, A. Celis, O. F Vazquez, and F. Rivas Genetic polymorphisms of the renin-angiotensin system in preterm delivery and premature rupture of membranes Journal of Renin-Angiotensin-Aldosterone System, December 1, 2007; 8(4): 160 - 168. [Abstract] [PDF]
|
|
|
|
|
|
C. J. Glueck, P. Wang, N. Goldenberg, and L. Sieve Pregnancy Loss, Polycystic Ovary Syndrome, Thrombophilia, Hypofibrinolysis, Enoxaparin, Metformin Clinical and Applied Thrombosis/Hemostasis, October 1, 2004; 10(4): 323 - 334. [Abstract] [PDF]
|
|