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Year 2014, , 350 - 355, 07.08.2014

Malik Yıldırım , Şeker Dağ Hande Kurtulgan , Savaş Karakuş

https://doi.org/10.7197/cmj.v36i3.5000060803
Cited By: 1

Abstract

Aim. Plasminogen activator inhibitor type 1 (PAI-1) is a serine protease inhibitor. It inhibits tissue plasminogen activator (tPA) and urokinase (uPA), and consequently inhibits fibrinolysis. There is a common polymorphism known as 4G/5G in the promoter region of PAI-1 gene. PAI-1 4G/4G polymorphism may contribute pregnancy complications because of its role in thrombosis,. In this study, we aimed to evaluate the possible effect of PAI-1 4G/4G polymorphism to miscarriages. Method. The study group was selected between individuals residing in Sivas region. One hundred and seventy eight women (92 of them have miscarriage story and 86 control) were incorporated to study. After DNA isolation, mutation analysis was performed by StripAssay technique based on the reverse-hybridization principle. Data were analysed by SPSS 15.0 statistic program. Results. In control group, the number of 5G/5G polymorphisms was 22 (25.6%), the number of 4G/5G polymorphisms was 53 (61.6%) and the number of 4G/4G mutant cases was 11 (12.8%). In miscarriage group, the number of 5G/5G polymorphisms was 20 (21.7%), the number of 4G/5G polymorphisms was 49 (53.3%) and the number of 4G/4G mutant cases was 23 (25%). ODDS ratio was calculated for 4G/4G homozygot mutant cases. Conclusion. According to our datas, 5G/5G and 4G/5G polymorphism have not higher risk for miscarriage (p=0.546 and p=0.259 p>0.05). In our study, it was detected that the contribution of 4G/4G polymorphism to miscarriage is important. The women who have this polymorphism carry the risk of miscarriage higher 2.27 fold (p=0.038 p<0.05).

Keywords

PAI-1 4G/4G polymorphism miscarriage

References

  • Mottonen J, Strand A, Symersky J, Sweet RM, Danley DE, Geoghegan KF, Gerard RD, Goldsmith EJ. Structural basis of latency in plasminogen activator inhibitor-1. Nature 1992: 355; 270-3.
  • Henry M, Chomiki N, Scarabin PY, Alessi MC, Peiretti F, Arveiler D FerrieresJ, Evans A, Amouyel P, Poirier O, Cambien F, Vague IJ. Five frequent polymorphisms of the PAI-1 gene lack of association between genotypes, PAI activity, and triglyceride levels in a healthy population. Arteriosclerosis, Thrombosis, and Vascular Biology 1997; 17: 851-8.
  • Magdoud K, Herbepin VG, Touraine R, Almawi WY, Mahjoub T. Plasminogen activator inhibitor 1 4G/5G and 844G/A variants in idiopathic recurrent pregnancy loss. American Journal of Reproductive Immunology 2013; 246-52.
  • Juhan-Vague I, Alessi MC. PAI-1, Obesity, insulin resistance and risk of cardiovascular events. Thromb Haemost 1997; 78: 656-60.
  • Attia J, Thakkinstian A, Wang Y, Lincz L, Parsons M, Sturm J, McGettigan P, Scott R, Meldrum C, Levi C. The PAI-1 4G/5G gene polymorphism and ischemic stroke: An association study and meta-analysis. J Stroke Cerebrovasc Dis 2007; 16: 173-9.
  • Su S, Chen S, Zhao J, Huang J, Wang X, Chen R, Gu D. Plasminogen activator inhibitor-1 gene selection of tagging single nucleotide polymorphisms and association with coronary heart disease.. Arteriosclerosis Thrombosis and Vascular Biology 2006; 26: 948-54.
  • MargaglioneM, Cappucci G, Colaizzo D, Giuliani N Vecchione G, Grandone E, Pennelli O, Di Minno G. The PAI-1 Gene Locus 4G/5G Polymorphism Is Associated With a Family history of coronary artery disease. Arteriosclerosis, Thrombosis, and Vascular Biology 1998; 18: 152-6.
  • Abboud N, Ghazouani L, Saidi S, Ben-Hadj-Khalifa S, Addad F, Almawi WY, Mahjoub T. Association of PAI-1 4G/5G and -844G/A gene polymorphisms and changes in PAI-1 /tissue plasminogen activator levels in myocardial infarction: A case-control study. Genet Test Mol Biomarkers 2010; 14: 23-7.
  • Isogai C, Laug WE, Shimada H, Declerck PJ, Stins MF, Durden DL, Anat Erdreich-Epstein, and De Clerck Y.A. Plasminogen activator inhibitor-1 promotes angiogenesis by stimulating endothelial cell migration toward fibronectin. Cancer Res 2001; 61: 5587.
  • Soltanghoraee H, Memariani T, Aarabi M, Hantoushzadeh S, Arefi S. Association of ACE, PAI-1 and coagulation factor XIII gene polymorphisms with recurrent spontaneous abortion in Iranian patients. Journal of Reproduction and Infertility 2007; 7: 29.
  • Parveen F, Tuteja M, Agrawal S. Polymorphisms in MTHFR, MTHFD, and PAI1 and recurrent miscarriage among north Indian women. Arch. Gynecol. Obstet 2013; 288: 1171-7.
  • Carp H, Salomon O, Seidman D, Dardik R, Rosenberg N, Inbal A. Prevalence of genetic markers for thrombophilia in recurrent pregnancy loss. Human Reproduction 2002; 17: 1633-7.
  • Dossenbach-Glaninger A, Trotsenburg M, Dossenbach M, Oberkanins C, Moritz A, Krugluger W, Huber J, Hopmeier P. Plasminogen activator inhibitor 1 4G/5G polymorphism and coagulation factor XIII Val34Leu polymorphism ımpaired fibrinolysis and early pregnancy loss. Clinical Chemistry 2003; 49: 1081-6.
  • Wolf CE, Haubelt H, Pauer HU, Hinney B, Krome-Cesar C, Legler TJ, Hellstern P, Emons G, Zoll B, Köhler M. 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: 134-7. Khaleghparast A, Morovvati S. Association between the PAI-1 4G/5G promoter polymorphism and recurrent miscarriage. Sci J Iran Blood Transfus Organ 2012; 9: 273-80.
  • Coulam CB, Jeyendran RS, Fishel LA, Roussev R. Multiple thrombophilic gene mutations rather than specific gene mutations are risk factors for recurrent miscarriage. American Journal of Reproductive Immunology 2006; 55: 360-8.
  • Reith A, Booth NA, Moore NR, Cruickshank DJ, Bennett B. Plasminogen activator inhibitors (PAI-1 and PAI-2) in normal pregnancies, pre-eclampsia and hydatidiform mole. Br J Obstet Gynaecol 1993; 100: 370-4.
  • Glueck CJ, Wang P, Fontaine RN, Sieve-Smith L, Tracy T, Moore SK. Plasminogen activator inhibitor activity: An independent risk factor for the high miscarriage rate during pregnancy in women with polycystic ovary syndrome. Metabolism 1999; 48: 1589-95.
  • 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: 2473-7.
  • Farhad Khosravi, Saeed Zarei, Negah Ahmadvand, Zahra Akbarzadeh-Pasha et al. Association between plasminogen activator inhibitor 1 gene mutation and different subgroups of recurrent miscarriage and implantation failure. J Assist Reprod. Genet 2014; 31: 121-4.
  • Glueck CJ, Kupferminc MJ, Fontaine RN, Wang P, Weksler BB, Eldor A. Genetic hypofibrinolysis in complicated pregnancies. Obstetrics and Gynecology 2001; 97: 44-8.

Plazminojen aktivatör inhibitor-1 (PAI-1) 4g/4g polimorfizminin gebelik kayıplarıyla ilişkisi

Year 2014, , 350 - 355, 07.08.2014

Malik Yıldırım , Şeker Dağ Hande Kurtulgan , Savaş Karakuş

https://doi.org/10.7197/cmj.v36i3.5000060803
Cited By: 1

Abstract

Özet

Amaç. Plazminojen aktivatör İnhibitörü Tip 1 (PAI-1) bir serin proteaz inhibitörüdür. Doku plazminojen aktivatörü (tPA) ve ürokinazı (uPA), sonuç olarak fibrinolizi inhibe eder. Genin promotor bölgesinde 4G/5G olarak bilinen bir polimorfizm söz konusudur. Trombozdaki rolü nedeniyle PAI-1 4G/4G polimorfizminin gebelik komplikasyonlarına katkısı olabileceği düşünülmektedir. Biz bu çalışmada, PAI-1 4G/4G polimorfizminin gebelik kayıplarına olası etkisini değerlendirmeyi amaçladık. Yöntem. Çalışma grubu Sivas bölgesinde yaşayan bireylerden seçildi. Araştırmaya 92’si bir veya daha fazla düşük öyküsü olan ve 86 kontrol olmak üzere toplam 178 kadın dahil edildi. Gen mutasyonlarını belirlemek için periferik kan örneklerinden DNA izolasyonu ve sonrasında revers hibridizasyon ilkesine dayanan strip assay tekniği ile mutasyon analizi yapıldı. Veriler SPSS 15,0 istatistik programı aracılığıyla değerlendirildi. Bulgular. Kontrol grubunda 5G/5G polimorfizmi 22 (%25,6), 4G/5G polimorfizmi 53 (%61,6) ve 4G/4G mutant olgular 11 (%12,8) olarak tespit edilmiştir. Düşük olgularında ise 5G/5G polimorfizmi 20 (%21,7), 4G/5G polimorfizmi 49 (53,3) ve 4G/4G mutant olgular ise 23 (%25) bulunmuştur. 4G/4G homozigot mutant olgular için ODDS değeri hesaplanmıştır. Sonuç. Bulgularımıza göre 5G/5G ve 4G/5G polimorfizmleri düşük açısından risk artışı sağlamamaktadır (p=0,546 ve p=0,259 p>0,05). Çalışmamızda PAI-1 4G/4G polimorfizminin düşük riskine katkısı anlamlı bulunmuştur. Bu polimorfizme sahip kadınlarda düşük yapma riski 2,27 kat daha fazladır (p=0,038 p<0,05).

Anahtar sözcükler: PAI-1, 4G/4G polimorfizmi, düşük

 

Abstract

Aim. Plasminogen activator inhibitor type 1 (PAI-1) is a serine protease inhibitor. It inhibits tissue plasminogen activator (tPA) and urokinase (uPA), and consequently inhibits fibrinolysis. There is a common polymorphism known as 4G/5G in the promoter region of PAI-1 gene. PAI-1 4G/4G polymorphism may contribute pregnancy complications because of its role in thrombosis,. In this study, we aimed to evaluate the possible effect of PAI-1 4G/4G polymorphism to miscarriages. Method. The study group was selected between individuals residing in Sivas region. One hundred and seventy eight women (92 of them have miscarriage story and 86 control) were incorporated to study. After DNA isolation, mutation analysis was performed by StripAssay technique based on the reverse-hybridization principle. Data were analysed by SPSS 15.0 statistic program. Results. In control group, the number of 5G/5G polymorphisms was 22 (25.6%), the number of 4G/5G polymorphisms was 53 (61.6%) and the number of 4G/4G mutant cases was 11 (12.8%). In miscarriage group, the number of 5G/5G polymorphisms was 20 (21.7%), the number of 4G/5G polymorphisms was 49 (53.3%) and the number of 4G/4G mutant cases was 23 (25%). ODDS ratio was calculated for 4G/4G homozygot mutant cases. Conclusion. According to our datas, 5G/5G and 4G/5G polymorphism have not higher risk for miscarriage (p=0.546 and p=0.259 p>0.05). In our study, it was detected that the contribution of 4G/4G polymorphism to miscarriage is important. The women who have this polymorphism carry the risk of miscarriage higher 2.27 fold (p=0.038 p<0.05).

Keywords: PAI-1, 4G/4G polymorphism, miscarriage

Keywords

PAI-1 4G/4G polimorfizmi düşük

References

  • Mottonen J, Strand A, Symersky J, Sweet RM, Danley DE, Geoghegan KF, Gerard RD, Goldsmith EJ. Structural basis of latency in plasminogen activator inhibitor-1. Nature 1992: 355; 270-3.
  • Henry M, Chomiki N, Scarabin PY, Alessi MC, Peiretti F, Arveiler D FerrieresJ, Evans A, Amouyel P, Poirier O, Cambien F, Vague IJ. Five frequent polymorphisms of the PAI-1 gene lack of association between genotypes, PAI activity, and triglyceride levels in a healthy population. Arteriosclerosis, Thrombosis, and Vascular Biology 1997; 17: 851-8.
  • Magdoud K, Herbepin VG, Touraine R, Almawi WY, Mahjoub T. Plasminogen activator inhibitor 1 4G/5G and 844G/A variants in idiopathic recurrent pregnancy loss. American Journal of Reproductive Immunology 2013; 246-52.
  • Juhan-Vague I, Alessi MC. PAI-1, Obesity, insulin resistance and risk of cardiovascular events. Thromb Haemost 1997; 78: 656-60.
  • Attia J, Thakkinstian A, Wang Y, Lincz L, Parsons M, Sturm J, McGettigan P, Scott R, Meldrum C, Levi C. The PAI-1 4G/5G gene polymorphism and ischemic stroke: An association study and meta-analysis. J Stroke Cerebrovasc Dis 2007; 16: 173-9.
  • Su S, Chen S, Zhao J, Huang J, Wang X, Chen R, Gu D. Plasminogen activator inhibitor-1 gene selection of tagging single nucleotide polymorphisms and association with coronary heart disease.. Arteriosclerosis Thrombosis and Vascular Biology 2006; 26: 948-54.
  • MargaglioneM, Cappucci G, Colaizzo D, Giuliani N Vecchione G, Grandone E, Pennelli O, Di Minno G. The PAI-1 Gene Locus 4G/5G Polymorphism Is Associated With a Family history of coronary artery disease. Arteriosclerosis, Thrombosis, and Vascular Biology 1998; 18: 152-6.
  • Abboud N, Ghazouani L, Saidi S, Ben-Hadj-Khalifa S, Addad F, Almawi WY, Mahjoub T. Association of PAI-1 4G/5G and -844G/A gene polymorphisms and changes in PAI-1 /tissue plasminogen activator levels in myocardial infarction: A case-control study. Genet Test Mol Biomarkers 2010; 14: 23-7.
  • Isogai C, Laug WE, Shimada H, Declerck PJ, Stins MF, Durden DL, Anat Erdreich-Epstein, and De Clerck Y.A. Plasminogen activator inhibitor-1 promotes angiogenesis by stimulating endothelial cell migration toward fibronectin. Cancer Res 2001; 61: 5587.
  • Soltanghoraee H, Memariani T, Aarabi M, Hantoushzadeh S, Arefi S. Association of ACE, PAI-1 and coagulation factor XIII gene polymorphisms with recurrent spontaneous abortion in Iranian patients. Journal of Reproduction and Infertility 2007; 7: 29.
  • Parveen F, Tuteja M, Agrawal S. Polymorphisms in MTHFR, MTHFD, and PAI1 and recurrent miscarriage among north Indian women. Arch. Gynecol. Obstet 2013; 288: 1171-7.
  • Carp H, Salomon O, Seidman D, Dardik R, Rosenberg N, Inbal A. Prevalence of genetic markers for thrombophilia in recurrent pregnancy loss. Human Reproduction 2002; 17: 1633-7.
  • Dossenbach-Glaninger A, Trotsenburg M, Dossenbach M, Oberkanins C, Moritz A, Krugluger W, Huber J, Hopmeier P. Plasminogen activator inhibitor 1 4G/5G polymorphism and coagulation factor XIII Val34Leu polymorphism ımpaired fibrinolysis and early pregnancy loss. Clinical Chemistry 2003; 49: 1081-6.
  • Wolf CE, Haubelt H, Pauer HU, Hinney B, Krome-Cesar C, Legler TJ, Hellstern P, Emons G, Zoll B, Köhler M. 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: 134-7. Khaleghparast A, Morovvati S. Association between the PAI-1 4G/5G promoter polymorphism and recurrent miscarriage. Sci J Iran Blood Transfus Organ 2012; 9: 273-80.
  • Coulam CB, Jeyendran RS, Fishel LA, Roussev R. Multiple thrombophilic gene mutations rather than specific gene mutations are risk factors for recurrent miscarriage. American Journal of Reproductive Immunology 2006; 55: 360-8.
  • Reith A, Booth NA, Moore NR, Cruickshank DJ, Bennett B. Plasminogen activator inhibitors (PAI-1 and PAI-2) in normal pregnancies, pre-eclampsia and hydatidiform mole. Br J Obstet Gynaecol 1993; 100: 370-4.
  • Glueck CJ, Wang P, Fontaine RN, Sieve-Smith L, Tracy T, Moore SK. Plasminogen activator inhibitor activity: An independent risk factor for the high miscarriage rate during pregnancy in women with polycystic ovary syndrome. Metabolism 1999; 48: 1589-95.
  • 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: 2473-7.
  • Farhad Khosravi, Saeed Zarei, Negah Ahmadvand, Zahra Akbarzadeh-Pasha et al. Association between plasminogen activator inhibitor 1 gene mutation and different subgroups of recurrent miscarriage and implantation failure. J Assist Reprod. Genet 2014; 31: 121-4.
  • Glueck CJ, Kupferminc MJ, Fontaine RN, Wang P, Weksler BB, Eldor A. Genetic hypofibrinolysis in complicated pregnancies. Obstetrics and Gynecology 2001; 97: 44-8.
There are 20 citations in total.

Details

Primary Language Turkish
Journal Section Medical Science Research Articles
Authors

Malik Yıldırım

Şeker Dağ

Hande Kurtulgan

Savaş Karakuş

Publication Date August 7, 2014
Published in Issue Year 2014

Cite

AMA Yıldırım M, Dağ Ş, Kurtulgan H, Karakuş S. Plazminojen aktivatör inhibitor-1 (PAI-1) 4g/4g polimorfizminin gebelik kayıplarıyla ilişkisi. CMJ. September 2014;36(3):350-355. doi:10.7197/cmj.v36i3.5000060803

Cited By

Güneydoğu Anadolu Bölgesi’ndeki Tekrarlayan Abortus Olgularında Protrombin, MTHFR, FV Leiden ve PAI-1 Polimorfizmlerinin Retrospektif Olarak İncelenmesi
Dicle Tıp Dergisi
Evren Gumus
https://doi.org/10.5798/dicletip.457243