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The 4G/5G polymorphism in the plasminogen activator inhibitor-1 gene is not associated with HELLP syndrome

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Abstract

Plasminogen activator inhibitor-1 (PAI-1) is a major inhibitor of fibrinolysis, and a single nucleotide insertion/deletion (4G/5G) polymorphism in the promoter region of the PAI-1 gene has been identified. Subjects homozygous for the 4G allele have the highest PAI-levels due to increased PAI-1 gene transcription. Pre-eclampsia, and one of its most severe forms, the HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome, are characterized by increased placental thrombosis based on a procoagulatory state in the mother. Several studies have investigated the role of the PAI-1 4G/5G polymorphism in pre-eclampsia, but no study has focused especially on HELLP syndrome. Therefore we aimed to assess the association between HELLP syndrome and the 4G/5G polymorphism in the PAI-1 gene. Genotyping of the PAI-1 4G/5G promoter polymorphism was performed in 102 Caucasian women with HELLP syndrome and 102 Caucasian women with uncomplicated pregnancies. The 4G/4G genotype was more frequent in women with HELLP syndrome than in controls (35.3% vs. 22.5%, respectively) but this difference was not significantly different (P = 0.129). The frequency of the 4G allele was 0.588 in patients and 0.515 in controls. These data suggest that women carrying a 4G/4G genotype of the PAI-1 gene are not at increased risk for developing HELLP syndrome and are thus in line with the majority of previous studies on the association between the PAI-1 4G/5G polymorphism and pre-eclampsia.

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References

  1. Rath W, Faridi A, Dudenhausen JW (2000) HELLP syndrome. J Perinat Med 28:249–260

    Article  PubMed  CAS  Google Scholar 

  2. Pridjian G, Puschett JB (2002) Preeclampsia. Part 1: clinical and pathophysiologic considerations. Obstet Gynecol Surv 57:598–618

    Article  PubMed  Google Scholar 

  3. Dellas C, Loskutoff DJ (2005) Historical analysis of PAI-1 from its discovery to its potential role in cell motility and disease. J Thromb Haemost 93:631–640

    CAS  Google Scholar 

  4. Ye Z, Liu EH, Higgins JP, Keavney BD, Lowe GD, Collins R, Danesh J (2006) Seven haemostatic gene polymorphisms in coronary disease: meta-analysis of 66,155 cases and 91,307 controls. Lancet 367:651–658

    Article  PubMed  CAS  Google Scholar 

  5. Dawson SJ, Wiman B, Hamsten A, Green F, Humphries S, Henney AM (1993) The two allele sequences of a common polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene respond differently to interleukin-1 in HepG2 cells. J Biol Chem 268:10739–10745

    PubMed  CAS  Google Scholar 

  6. Wiwanitkit V (2006) Correlation between plasminogen activator inhibitor-1 4G/5G polymorphism and pre-eclampsia: an appraisal. Arch Gynecol Obstet 273:322–324

    Article  PubMed  Google Scholar 

  7. Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215

    Article  PubMed  CAS  Google Scholar 

  8. Falk G, Almqvist A, Nordenhem A, Svensson H, Wiman B (1995) Allele-specific PCR for detection of a sequence polymorphism in the promoter region of the plasminogen activator inhibitor-1 (PAI-1) gene. Fibrinolysis 9:170–174

    Article  CAS  Google Scholar 

  9. Yamada N, Arinami T, Yamakawa-Kobayashi K, Watanabe H, Sohda S, Hamada H, Kubo T, Hamaguchi H (2000) The 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene is associated with severe preeclampsia. J Hum Genet 45:138–141

    Article  PubMed  CAS  Google Scholar 

  10. Fabbro D, D’Elia AV, Spizzo R, Driul L, Barillari G, Di LC, Marchesoni D, Damante G (2003) Association between plasminogen activator inhibitor 1 gene polymorphisms and preeclampsia. Gynecol Obstet Invest 56:17–22

    Article  PubMed  CAS  Google Scholar 

  11. Glueck CJ, Kupferminc MJ, Fontaine RN, Wang P, Weksler BB, Eldor A (2001) Genetic hypofibrinolysis in complicated pregnancies. Obstet Gynecol 97:44–48

    Article  PubMed  CAS  Google Scholar 

  12. Dalmaz CA, Santos KG, Botton MR, Tedoldi CL, Roisenberg I (2006) Relationship between polymorphisms in thrombophilic genes and preeclampsia in a Brazilian population. Blood Cells Mol Dis 37:107–110

    Article  PubMed  CAS  Google Scholar 

  13. De Maat MP, Jansen MW, Hille ET, Vos HL, Bloemenkamp KW, Buitendijk S, Helmerhorst FM, Wladimiroff JW, Bertina RM, de Groot CJ (2004) Preeclampsia and its interaction with common variants in thrombophilia genes. J Thromb Haemost 2:1588–1593

    Article  PubMed  Google Scholar 

  14. Gerhardt A, Goecke TW, Beckmann MW, Wagner KJ, Tutschek B, Willers R, Bender HG, Scharf RE, Zotz RB (2005) The G20210A prothrombin-gene mutation and the plasminogen activator inhibitor (PAI-1) 5G/5G genotype are associated with early onset of severe preeclampsia. J Thromb Haemost 3:686–691

    Article  PubMed  CAS  Google Scholar 

  15. Hakli T, Romppanen EL, Hiltunen M, Helisalmi S, Punnonen K, Heinonen S (2003) Plasminogen activator inhibitor-1 polymorphism in women with pre-eclampsia. Genet Test 7:265–268

    Article  PubMed  Google Scholar 

  16. Kobashi G (2006) Genetic and environmental factors associated with the development of hypertension in pregnancy. J Epidemiol 16:1–8

    Article  PubMed  Google Scholar 

  17. Morrison ER, Miedzybrodzka ZH, Campbell DM, Haites NE, Wilson BJ, Watson MS, Greaves M, Vickers MA (2002) Prothrombotic genotypes are not associated with pre-eclampsia and gestational hypertension: results from a large population-based study and systematic review. J Thromb Haemost 87:779–785

    CAS  Google Scholar 

  18. Pegoraro RJ, Hira B, Rom L, Moodley J (2003) Plasminogen activator inhibitor type 1 (PAI1) and platelet glycoprotein IIIa (PGIIIa) polymorphisms in Black South Africans with pre-eclampsia. Acta Obstet Gynecol Scand 82:313–317

    Article  PubMed  Google Scholar 

  19. Tempfer CB, Jirecek S, Riener EK, Zeisler H, Denschlag D, Hefler L, Husslein PW (2004) Polymorphisms of thrombophilic and vasoactive genes and severe preeclampsia: a pilot study. J Soc Gynecol Investig 11:227–231

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Sabine Muetze.

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Muetze, S., Eggermann, T., Leeners, B. et al. The 4G/5G polymorphism in the plasminogen activator inhibitor-1 gene is not associated with HELLP syndrome. J Thromb Thrombolysis 27, 141–145 (2009). https://doi.org/10.1007/s11239-007-0175-9

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  • DOI: https://doi.org/10.1007/s11239-007-0175-9

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