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

Soltanghoraee, Haleh; Memariani, Taktom; Aarabi, Mahmood; Hantoushzadeh, Sedigheh; Arefi, Soheila; Aarabi, Mohsen; Akhondi, Mohammad Mehdi; Modarresi, Mohammad Hossein

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

Recurrent spontaneous abortion

Thrombophilia

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.

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.

Walker ID. Thrombophilia in pregnancy. J Clin Pathol. 2000;53:573-580.

Kupferminc MJ. Thrombophilia and pregnancy. Reprod Biol Endocrinol. 2003;1:111.

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.

Buchholz T, Thaler CJ. Inherited thrombophilia: impact on human reproduction. Am J Reprod Immunol. 2003; 49:1-13.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Charles J, Glueck MD, Michael J, Kupferminc MD. Genetic Hypofibrinolysis in Complicated Pregnancies. Obstet Gynecol. 2001;97:44-48.

Badenhop RF, Wang XL, Wilcken DE. Angiotensin-converting enzyme genotype in children and coronary events in their grandparents. Circulation. 1995;91(6): 1655-8.

Bereczky Z, Katona E, Muszbek L. Fibrin Stabiliza-tion (Factor XIII), Fibrin Structure and Thrombosis. Pathophysiol Haemost Thromb. 2003/2004;33:430-7.

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.

Kohler HP. Role of blood coagulation factor XIII in vascular diseases. Swiss Med Wkly. 2001;27:131(3-4):31-4.

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.

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.

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.

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.

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.