Volume 13, Issue 10 (10-2015)                   IJRM 2015, 13(10): 627-632 | Back to browse issues page

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Shakarami F, Taghi Akbari M, Zare Karizi S. Association of plasminogen activator inhibitor-1 (PAI-1) and angiotensin converting enzyme polymorphisms with recurrent pregnancy loss in Iranian women. IJRM 2015; 13 (10) :627-632
URL: http://ijrm.ir/article-1-595-en.html
1- Department of Biology, Guilan University, Rasht, Iran
2- Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran , mtakbari@modares.ac.ir
3- Department of Biology, Varamin Pishva Branch, Islamic Azad University, Varamin Pishva, Iran
Abstract:   (3503 Views)
Background: Recurrent pregnancy loss (RPL) defined by two or more failed pregnancies before 20 weeks of gestation. Several factors play a role in RPL including thrombophilic conditions which can be influenced by gene polymorphisms. Plasminogen activator inhibitor-1 (PAI-1) and angiotensin converting enzyme (ACE) genes are closely related to fibrinolytic process, embryonic development and pregnancy success.
Objective: The aim of this study was to investigate the relationship between RPL and common polymorphisms in ACE and PAI-1 genes.
Materials and Methods: In this case control study, 100 women with recurrent abortions (at least two) were selected as cases and 100 healthy women with two or more normal term deliveries without a history of abortion as controls. Total genomic DNA was isolated from blood leukocytes. The status of the PAI-1 4G/5G and ACE (D/I) polymorphism was determined by PCR-RFLP.
Results: Homozygosity for PAI-1 4G polymorphism was seen in 17 cases (17%), and 5 controls (5%) (p=0.006) so patients with homozygote 4G mutation were significantly more prone to RPL in contrast to control group (OR: 4.63, % 95 CI: 1.55-13.84). In addition, 7 patients (7 %), and no one from the control group, were homozygote (I/I) for ACE polymorphism (p=0.034), suggesting no significant associations between ACE D allele or DD genotype and RPL.
Conclusion: Considering these results, because 4G/4G polymorphism for PAI-1 gene could be a thrombophilic variant leading to abortion, analysis of this mutation and other susceptibility factors are recommended in patients with RPL.
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Type of Study: Original Article |

References
1. Tulandi T, Huang JY, Tan SL. Preservation of female fertility: an essential progress. Obstet Gynecol 2008; 112: 1160-1172. [DOI:10.1097/AOG.0b013e31818bba31]
2. Christiansen OB, Nielsen HS, Kolte A, Pedersen AT. Research Methodology and Epidemiology of Relevance in Recurrent Pregnancy Loss. Semin Reprod Med 2006; 24: 5–16. [DOI:10.1055/s-2006-931796]
3. Franssen MT, Korevaar JC, Leschot NJ, Bossuyt PM, Knegt AC, Gerssen-Schoorl KB, et al. Selective chromosome analysis in couples with two or more miscarriages: case-control study. BMJ 2005; 331: 137–141. [DOI:10.1136/bmj.38498.669595.8F]
4. Kuhli C, Luchtenberg M, Scharrer I, Hattenbach LO. Massive subhyaloidal hemorrhage associated with severe PAI-1 deficiency. Graefes Arch Clin Exp Ophthalmol 2005; 243: 963–966. [DOI:10.1007/s00417-005-0048-x]
5. Festa A, D'Agostino R Jr, Rich SS, Jenny NS, Tracy RP, Haffner SM. Promoter (4G ⁄ 5G) plasminogen activator inhibitor-1 genotype and plasminogen activator-1 levels in blacks, Hispanics and non Hispanic whites: the Insulin Resistance Atherosclerosis Study. Circulation 2003; 107: 2422-2427. [DOI:10.1161/01.CIR.0000066908.82782.3A]
6. Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion/deletion polymorphism in the angiotensin I converting enzyme gene accounts for half the variance of serum enzyme levels. J Clin Invest 1990; 86: 1343–1346. [DOI:10.1172/JCI114844]
7. Asgari N, Akbari MT, Zare S, Babamohammadi G. Positive association of Apolipoprotein E4 polymorphism with recurrent pregnancy loss in Iranian patients. J Assist Reprod Genet 2013; 30: 265–268. [DOI:10.1007/s10815-012-9897-5]
8. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16: 1215-1220. [DOI:10.1093/nar/16.3.1215]
9. Buchholz T, Lohse P, Rogenhofer N, Kosian E, Pihusch R, Thaler CJ. Polymorphisms in the ACE and PAI-1 genes are associated with recurrent spontaneous miscarriages. Hum Reprod 2003; 18: 2473–2477. [DOI:10.1093/humrep/deg474]
10. Dossenbach-Glaninger A, Van Trotsenburg M, Dossenbach M, Oberkanins C, Moritz A, Krugluger W, et al. Plasminogen activator inhibitor 1 4G/5G polymorphism and coagulation factor XIII Val34Leu polymorphism: impaired fibrinolysis and early pregnancy loss. Clin Chem 2003; 49: 1081-1086. [DOI:10.1373/49.7.1081]
11. Soltan ghoraei H, Memariani T, Aarabi M, Arefi SS, Hantoushzadeh S, Aarabi M, et al. Association of ACE, PAI-1 and coagulation factor XIII gene polymorphisms with recurrent spontaneous abortion in Iranian patients. J Reprod Infertil 2007; 4: 2324-2330.
12. Aarabi M, Memariani T, Arefi S, Aarabi M, Hantoosh Zadeh S, Akhondi MA, et al. Polymorphisms of plasminogen activator inhibitor-1, angiotensin converting enzyme and coagulation factor XIII genes in patients with recurrent spontaneous abortion. J Matern Fetal Neonatal Med 2011; 24: 545-548. [DOI:10.3109/14767058.2010.511331]
13. Guan LX, Du XY, Wang JX, Gao L, Wang RL, Li HB, et al. Association of genetic polymorphisms in plasminogen activator inhibitor-1 gene and 5, 10-methylenetetrahydrofolate reductase gene with recurrent early spontaneous abortion. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2005; 22: 330-333.
14. Al Sallout RJ, Sharif FA. Polymorphisms in NOS3, ACE and PAI-1 genes and risk of spontaneous recurrent miscarriage in the Gaza Strip. Med Princ Pract 2010; 19: 99-104. [DOI:10.1159/000273067]
15. Ivanov P, Komsa-Penkova R, Konova E, Gecheva S, Ivanov I, Kovacheva K, et al. Combined thrombophilic factors among women with late recurrent spontaneous abortions. Akusherstvo iginekologiia 2011; 50: 8-12.
16. Coulam CB, Jeyendran RS, Fishel LA, Roussev R. Multiple thrombophilic gene mutations are risk factors for implantation failure. Reprod Biomed Online 2006; 12: 322-327. [DOI:10.1016/S1472-6483(10)61004-8]
17. Coulam CB, Jeyendran RS. Thrombophilic gene polymorphisms are risk factors for unexplained infertility. Fertil Steril 2009; 91: 1516-1517. [DOI:10.1016/j.fertnstert.2008.07.1782]
18. Wolf CE, Haubelt H, Pauer HU, Hinney B, Krome-Cesar C, Legler TJ, et al. Recurrent pregnancy loss and its relation to FV Leiden, FII G20210A and polymorphisms Of plasminogen activator and plasminogen activator inhibitor. Pathophysiol Haemost Thromb 2003; 33: 134-137. [DOI:10.1159/000077821]
19. Schenk JF, Stephan B, Zewinger S, Speer T, Pindur G. Comparison of the plasminogen activator inhibitor-1 4G/5G gene polymorphism in females with venous thromboembolism during pregnancy or spontaneous abortion. Clin Hemorheol Microcirc 2008; 39: 329-332.
20. Su MT, Lin SH, Chen YC, Kuo PL. Genetic association studies of ACE and PAI-1 genes in women with recurrent pregnancy loss: a systematic review and meta-analysis. Thromb Haemost 2012; 109: 8-15. [DOI:10.1160/TH12-08-0584]

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