Journal of Reproduction & Infertility

Journal of Reproduction & Infertility

Association of ACE, PAI-1 and coagulation factor XIII gene polymorphisms with recurrent spontaneous abortion in Iranian patients

Authors
Haleh Soltanghoraee 1
Taktom Memariani 2
Mahmood Aarabi 2
Sedigheh Hantoushzadeh 3
Soheila Arefi 1
Mohsen Aarabi 4
Mohammad Mehdi Akhondi 5
Mohammad Hossein Modarresi 6
1 Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran; Avicenna Infertility Clinic, Avicenna Research Institute (ACECR), Tehran, Iran
2 Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
3 Faculty of Medical Tehran University of Medical Sciences, Tehran, Iran
4 Academic Unit of clinical Pharmacology ,University of Sheffield, Sheffield, United Kingdom
5 Monoclonal Antibody Research Center, Avicenna Research Institute (ACECR), Tehran, Iran
6 Faculty of Medical Tehran University of Medical Sciences, Tehran, Iran; Nanobiotechnology Research Center, Avicenna Research Institute (ACECR), Tehran, Iran
Abstract
Introduction: Considering the 5% prevalence of abortion in women, its devastating psycholo-gical effects on affected people’s lives and as tendency for clotting is one of the causes of recur-rent spontaneous abortion (RSA), this study was designed to compare plasminogen activator inhibitor-1 (PAI-1), angiotensin converting enzyme (ACE) and blood coagulation factor XIII (FXIII) gene polymorphisms in Iranian patients with RSA and healthy women. Materials & Methods: 120 patients with recurrent abortions (at least two) as cases and 112 healthy female controls without a history of abortion were entered into the study. In order to characterize PAI-1 (4G/5G), ACE (D/I) and FXIII (Val 34 Leu) polymorphisms, a polymerase chain reaction followed by digestion with restriction enzymes (PCR-RFLP) was designed. For the statistical analysis, SPSS software version 11.2 was used and t-test, Chi-square and Fisher’s exact tests were calculated. P-values
Keywords
Angiotensin Converting Enzyme
Coagulation factor XIII
Plasminogen activator inhibitor
1
Recurrent spontaneous abortion
Thrombophilia
  1. 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(11):2473-2477.
  2. Bick RL. Recurrent miscarriage syndrome due to blood coagulation protein/platelet defects: prevalence, treat-ment and outcome results. DRW Metroplex Recurrent Miscarriage Syndrome Cooperative Group. Clin Appl Thromb Hemost. 2000;6(3):115-25.
  3. Walker ID. Thrombophilia in pregnancy. J Clin Pathol. 2000;53:573-580.
  4. Kupferminc MJ. Thrombophilia and pregnancy. Reprod Biol Endocrinol. 2003;1:111.
  5. Kempf Haber M, Klimek M. Thrombophilia in preg-nancy and its influence on venous thromboembolism and recurrent miscarriages. Przegl Lek. 2005;62(3): 164-8.
  6. Buchholz T, Thaler CJ. Inherited thrombophilia: impact on human reproduction. Am J Reprod Immunol. 2003; 49:1-13.
  7. Abbate R, Sofi F, Gensini F, Fatini C, Sticchi E, Fedi S. Thrombophilias as risk factors for disorders of pregnancy and fetal damage. Pathophysiol Haemost Thromb. 2002;32:318-321.
  8. Bick RL, Hoppensteadt D. Recurrent miscarriage syndrome and infertility due to blood coagulation protein/platelet defects: a review and update. Clin Appl Thromb Hemost. 2005;11(1):1-13.
  9. Pickering W, Marriott K, Regan L. G20210A pro-thrombin gene mutation: prevalence in a recurrent miscarriage population. Clin Appl Thromb Hemost. 2001;7(1):25-8.
  10. Lissalde-Lavigne G, Fabbro-Peray P. Factor V Leiden and prothrombin G20210A polymorphisms as risk factors for miscarriage during a first intended pregnancy: the matched case-control 'NOHA first' study. J Thromb Haemost. 2005;3(10):2178-84.
  11. Mtiraoui N, Borgi L, Hizem S, Nsiri B, Finan RR, Gris JC, et al. Prevalence of antiphospholipid anti-bodies, factor V G1691A (Leiden) and prothrombin G20210A mutations in early and late recurrent pregnancy loss. Eur J Obstet Gynecol Reprod Biol. 2005;119(2):164-70.
  12. Mjoub T, Mtiraoui N, Tamim H, Hizem S, Finan RR, Nsiri B, et al. Association between adverse pregnancy outcomes and maternal factor V G1691A (Leiden) and prothrombin G20210A genotypes in women with a history of recurrent idiopathic miscarriages .Am J Hematol. 2005;80(1):12-9.
  13. Couto E, Barini R, Zaccaria R. Association of anticar-diolipin antibody and C677T in methylenetetrahydro-folate reductase mutation in women with recurrent spontaneous abortions: a new path to thrombophilia?. Sao Paulo Med J. 2005;123 (1):15-20.
  14. Mtiraoui N, Zammiti W, Ghazouani L. Methylenetet-rahydrofolate reductase C677T and A1298C polymer-phism and changes in homocysteine concentrations in women with idiopathic recurrent pregnancy losses. Rep-roduction. 2006;131(2):395-401.
  15. Glueck CJ, Wang P, Goldenberg N, Sieve L. Pregnan-cy loss, polycystic ovary syndrome, thrombophilia, hypofibrinolysis, enoxaparin, metformin. Clin Appl Thromb Hemost. 2004;10(4): 323-34.
  16. Kotze MJ, La Grange C, Mansvelt EPG. Rapid throm-bophilia genetic test facilitates prenatal care for mother and child .SA Fam Pract. 2005;47(7):50-51.
  17. Tsanadis G, Vartholomatos I, Korkontzelos F, Av-goustatos G, Kakosimos A, Sotiriadis A et al. Poly-cystic ovarian syndrome and thrombophilia. Hum Reprod. 2002;17(2):314-319.
  18. Balta G, Altay C, Gurgey A. PAI-1 Gene 4G/5G Genotype: A Risk Factor for Thrombosis in Vessels of Internal Organs. Am J Hematol. 2002;71:89-93.
  19. Charles J, Glueck MD, Michael J, Kupferminc MD. Genetic Hypofibrinolysis in Complicated Pregnancies. Obstet Gynecol. 2001;97:44-48.
  20. Badenhop RF, Wang XL, Wilcken DE. Angiotensin-converting enzyme genotype in children and coronary events in their grandparents. Circulation. 1995;91(6): 1655-8.
  21. Bereczky Z, Katona E, Muszbek L. Fibrin Stabiliza-tion (Factor XIII), Fibrin Structure and Thrombosis. Pathophysiol Haemost Thromb. 2003/2004;33:430-7.
  22. Karpati L, Penke B, Katona E, Balogh I, Vamosi G, Muszbek L. A Modified, Optimized Kinetic Photo-metric Assay for the Determination of Blood Coagu-lation Factor XIII Activity in Plasma. Clin Chem. 2000;46:1946-1955.
  23. Kohler HP. Role of blood coagulation factor XIII in vascular diseases. Swiss Med Wkly. 2001;27:131(3-4):31-4.
  24. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nuclea-ted cells. Nucleic Acids Res. 1988;11;16(3):1215.
  25. Reiner AP, Schwartz SM, Frank MB, Longstreth WT Jr, Hindorff LA., Teramura G, et al . Polymorphisms of coagulation factor XIII subunit A and risk of nonfatal hemorrhagic stroke in young white women. Stroke. 2001;32(11):2580-6.
  26. Fatini C, Gensini F, Battaglini B, Prisco D, Cellai AP, Fedi S,et al. Angiotensin-converting enzyme DD geno-type, angiotensin type 1 receptor CC genotype, and hyperhomocysteinemia increase first-trimester fetal-loss susceptibility. Blood Coagul Fibrinolysis. 2000;11 (7):657-62.
  27. Gris JC, Neveu S, Mares P, Biron C, Hedon B, Schved JF. Plasma fibrinolytic activators and their inhibitors in women suffering from early recurrent abortion of unknown etiology. J Lab Clin Med. 1993; 122(5):606-15.
  28. Glueck CJ, Wang P, Fontaine RN, Sieve-Smith L, Tracy T, Moore SK. Plasminogen activator inhibitor activity: an independent risk factor for the high mis-carriage rate during pregnancy in women with poly-cystic ovary syndrome. Metabolism. 1999;48(12): 1589-95.
  29. Wiwanitkit V. Angiotensin-converting enzyme gene polymorphism: I and D alleles from some different countries. Clin Appl Thromb Hemost. 2004;10(2):179-82.
  30. Mello G, Parretti E, Gensini F, Sticchi E, Mecacci F, Scarselli G, et al. Maternal-fetal flow, negative events, and preeclampsia: role of ACE I/D polymorphism. Hypertension. 2003; 41(4):932-7.
  31. Barley J, Blackwood A, Carter ND, Crews DE, Cruickshank JK, Jeffery S, et al. Angiotensin conver-ting enzyme insertion/deletion polymorphism: Associa-tion with ethnic origin. J Hypertens. 1994;12:955.
  32. Behjati R, Modarressi MH, Jeddi-Tehrani M, Dokoo-haki P, Ghasemi J, Zarnani AH, et al. Thrombophilic mutations in Iranian patients with infertility and recurrent spontaneous abortion. Ann Hematol. 2006; 85(4):268-71.
Journal of Reproduction & Infertility
Volume 7, Issue 4
Winter 2007
Pages 324-330