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Semin Thromb Hemost 2011; 37(2): 097-105
DOI: 10.1055/s-0030-1270334
© Thieme Medical Publishers

Plasminogen Activator Inhibitor-1 Gene Polymorphisms in Pre-Eclampsia

Angela V. D'Elia1 , Dora Fabbro1 , Lorenza Driul2 , Giovanni Barillari3 , Diego Marchesoni2 , Giuseppe Damante1 , 4
  • 1Istituto di Genetica Medica – AOUSMM Udine, at Udine, Italy
  • 2Dipartimento di Scienze Chirurgiche – Università di Udine, at Udine, Italy
  • 3Istituto di Medicina Trasfusionale – AOUSMM Udine, at Udine, Italy
  • 4Dipartimento di Scienze e Tecnologie Biomediche – Università di Udine, at Udine, Italy
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Publikationsverlauf

Publikationsdatum:
02. März 2011 (online)

    Lizenzen und Reprints

ABSTRACT

Pre-eclampsia (P-EC) is a multisystem disorder of pregnancy, characterized by new-onset hypertension and proteinuria. Deregulation of the coagulation cascade and hypofibrinolysis appear to play a central role in the development of this disease. After a brief review of the genetic basis of P-EC and the role of genes encoding proteins involved in coagulation, we focus on polymorphisms of the plasminogen activator inhibitor (PAI-1) gene. The most relevant association studies between PAI-1 gene polymorphisms and P-EC are reviewed. Results indicate that the 4G/4G genotype of the -675 4G/5G polymorphism represents a weak risk factor for P-EC.

KEYWORDS

Pre-eclampsia - gene polymorphisms - PAI-1

REFERENCES

  • 1 Sibai B M, Ewell M, Levino R J et al.. Risk factors associated with preeclampsia in healthy nulliparous women. The Calcium for Preeclampsia Prevention (CPEP) Study Group.  Am J Obstet Gynecol. 1997;  177 1003-1010
    CrossrefPubMedGoogle Scholar
  • 2 Dekker G A, Sibai B M. Etiology and pathogenesis of preeclampsia: current concepts.  Am J Obstet Gynecol. 1998;  179 (5) 1359-1375
    CrossrefPubMedGoogle Scholar
  • 3 Sibai B, Dekker G, Kupferminc M. Pre-eclampsia.  Lancet. 2005;  365 (9461) 785-799
    CrossrefPubMedGoogle Scholar
  • 4 Kruithof E KO, Tran-Thang C, Gudinchet A et al.. Fibrinolysis in pregnancy: a study of plasminogen activator inhibitors.  Blood. 1987;  69 (2) 460-466
    PubMedGoogle Scholar
  • 5 Estellés A, Gilabert J, Aznar J, España F, Schleef R, Loskutoff D J. Cellular expression and potential roles of plasminogen activator inhibitors in normal and pathological pregnancies. In: Aznar J, Gilabert J, Estellés A Fibrinolytic Inhibitors. Cellular, Biological and Clinical Aspects. Madrid, Spain: Garsi-Masson; 1994: 43-59
    Google Scholar
  • 6 He S, Bremme K, Blombäck M. Increased blood flow resistance in placental circulation and levels of plasminogen activator inhibitors types 1 and 2 in severe preeclampsia.  Blood Coagul Fibrinolysis. 1995;  6 (8) 703-708
    CrossrefPubMedGoogle Scholar
  • 7 Graeff H, von Hugo R, Schröck R. Recent aspects of hemostasis, hematology and hemorheology in preeclampsia-eclampsia.  Eur J Obstet Gynecol Reprod Biol. 1984;  17 (2–3) 91-102
    CrossrefPubMedGoogle Scholar
  • 8 Friedman S A, Schiff E, Emeis J J, Dekker G A, Sibai B M. Biochemical corroboration of endothelial involvement in severe preeclampsia.  Am J Obstet Gynecol. 1995;  172 (1 Pt 1) 202-203
    CrossrefPubMedGoogle Scholar
  • 9 Gao M, Nakabayashi M, Sakura M, Takeda Y. The imbalance of plasminogen activators and inhibitor in preeclampsia.  J Obstet Gynaecol Res. 1996;  22 (1) 9-16
    PubMedGoogle Scholar
  • 10 Teng Y C, Lin Q D, Lin J H, Ding C W, Zuo Y. Coagulation and fibrinolysis related cytokine imbalance in preeclampsia: the role of placental trophoblasts.  J Perinat Med. 2009;  37 (4) 343-348
    PubMedGoogle Scholar
  • 11 Arngrimsson R, Björnsson S, Geirsson R T, Björnsson H, Walker J J, Snaedal G. Genetic and familial predisposition to eclampsia and pre-eclampsia in a defined population.  Br J Obstet Gynaecol. 1990;  97 (9) 762-769
    PubMedGoogle Scholar
  • 12 Folgerø T, Storbakk N, Torbergsen T, Oian P. Mutations in mitochondrial transfer ribonucleic acid genes in preeclampsia.  Am J Obstet Gynecol. 1996;  174 (5) 1626-1630
    CrossrefPubMedGoogle Scholar
  • 13 Reich D E, Lander E S. On the allelic spectrum of human disease.  Trends Genet. 2001;  17 (9) 502-510
    CrossrefPubMedGoogle Scholar
  • 14 Mogren I, Högberg U, Winkvist A, Stenlund H. Familial occurrence of preeclampsia.  Epidemiology. 1999;  10 (5) 518-522
    CrossrefPubMedGoogle Scholar
  • 15 Nilsson E, Salonen Ros H, Cnattingius S, Lichtenstein P. The importance of genetic and environmental effects for pre-eclampsia and gestational hypertension: a family study.  BJOG. 2004;  111 (3) 200-206
    PubMedGoogle Scholar
  • 16 Dawson L M, Parfrey P S, Hefferton D et al.. Familial risk of preeclampsia in Newfoundland: a population-based study.  J Am Soc Nephrol. 2002;  13 (7) 1901-1906
    CrossrefPubMedGoogle Scholar
  • 17 Cincotta R B, Brennecke S P. Family history of pre-eclampsia as a predictor for pre-eclampsia in primigravidas.  Int J Gynaecol Obstet. 1998;  60 (1) 23-27
    CrossrefPubMedGoogle Scholar
  • 18 Plunkett J, Borecki I, Morgan T, Stamilio D, Muglia L J. Population-based estimate of sibling risk for preterm birth, preterm premature rupture of membranes, placental abruption and pre-eclampsia.  BMC Genet. 2008;  9 44
    PubMedGoogle Scholar
  • 19 Lachmeijer A M, Aarnoudse J G, ten Kate L P, Pals G, Dekker G A. Concordance for pre-eclampsia in monozygous twins.  Br J Obstet Gynaecol. 1998;  105 (12) 1315-1317
    PubMedGoogle Scholar
  • 20 O'Shaughnessy K M, Ferraro F, Fu B, Downing S, Morris N H. Identification of monozygotic twins that are concordant for preeclampsia.  Am J Obstet Gynecol. 2000;  182 (5) 1156-1157
    CrossrefPubMedGoogle Scholar
  • 21 Salonen Ros H, Lichtenstein P, Lipworth L, Cnattingius S. Genetic effects on the liability of developing pre-eclampsia and gestational hypertension.  Am J Med Genet. 2000;  91 (4) 256-260
    CrossrefPubMedGoogle Scholar
  • 22 Thornton J G, Macdonald A M. Twin mothers, pregnancy hypertension and pre-eclampsia.  Br J Obstet Gynaecol. 1999;  106 (6) 570-575
    PubMedGoogle Scholar
  • 23 Treloar S A, Cooper D W, Brennecke S P, Grehan M M, Martin N G. An Australian twin study of the genetic basis of preeclampsia and eclampsia.  Am J Obstet Gynecol. 2001;  184 (3) 374-381
    CrossrefPubMedGoogle Scholar
  • 24 Esplin M S, Fausett M B, Fraser A et al.. Paternal and maternal components of the predisposition to preeclampsia.  N Engl J Med. 2001;  344 (12) 867-872
    CrossrefPubMedGoogle Scholar
  • 25 Cnattingius S, Reilly M, Pawitan Y, Lichtenstein P. Maternal and fetal genetic factors account for most of familial aggregation of preeclampsia: a population-based Swedish cohort study.  Am J Med Genet A. 2004;  130A (4) 365-371
    CrossrefPubMedGoogle Scholar
  • 26 Nejatizadeh A, Stobdan T, Malhotra N, Pasha M A. The genetic aspects of pre-eclampsia: achievements and limitations.  Biochem Genet. 2008;  46 (7-8) 451-479
    CrossrefPubMedGoogle Scholar
  • 27 Chappell S, Morgan L. Searching for genetic clues to the causes of pre-eclampsia.  Clin Sci (Lond). 2006;  110 (4) 443-458
    CrossrefPubMedGoogle Scholar
  • 28 Dekker G A. Risk factors for preeclampsia.  Clin Obstet Gynecol. 1999;  42 (3) 422-435
    CrossrefPubMedGoogle Scholar
  • 29 Dekker G. Prothrombotic mechanisms in preeclampsia.  Thromb Res. 2005;  115 (Suppl 1) 17-21
    PubMedGoogle Scholar
  • 30 Kupferminc M J, Eldor A, Steinman N et al.. Increased frequency of genetic thrombophilia in women with complications of pregnancy.  N Engl J Med. 1999;  340 (1) 9-13
    CrossrefPubMedGoogle Scholar
  • 31 van Pampus M G, Dekker G A, Wolf H et al.. High prevalence of hemostatic abnormalities in women with a history of severe preeclampsia.  Am J Obstet Gynecol. 1999;  180 (5) 1146-1150
    CrossrefPubMedGoogle Scholar
  • 32 Dizon-Townson D S, Nelson L M, Easton K, Ward K. The factor V Leiden mutation may predispose women to severe preeclampsia.  Am J Obstet Gynecol. 1996;  175 (4 Pt 1) 902-905
    CrossrefPubMedGoogle Scholar
  • 33 Nagy B, Tóth T, Rigó Jr J J, Karádi I, Romics L, Papp Z. Detection of factor V Leiden mutation in severe pre-eclamptic Hungarian women.  Clin Genet. 1998;  53 (6) 478-481
    CrossrefPubMedGoogle Scholar
  • 34 Mello G, Parretti E, Marozio L et al.. Thrombophilia is significantly associated with severe preeclampsia: results of a large-scale, case-controlled study.  Hypertension. 2005;  46 1270-1274
    CrossrefPubMedGoogle Scholar
  • 35 Kim Y J, Williamson R A, Murray J C et al.. Genetic susceptibility to preeclampsia: roles of cytosineto-thymine substitution at nucleotide 677 of the gene for methylenetetrahydrofolate reductase, 68-base pair insertion at nucleotide 844 of the gene for cystathionine beta-synthase, and factor V Leiden mutation.  Am J Obstet Gynecol. 2001;  184 (6) 1211-1217
    CrossrefPubMedGoogle Scholar
  • 36 Livingston J C, Barton J R, Park V, Haddad B, Phillips O, Sibai B M. Maternal and fetal inherited thrombophilias are not related to the development of severe preeclampsia.  Am J Obstet Gynecol. 2001;  185 (1) 153-157
    CrossrefPubMedGoogle Scholar
  • 37 Grandone E, Margaglione M, Colaizzo D et al.. Prothrombotic genetic risk factors and the occurrence of gestational hypertension with or without proteinuria.  Thromb Haemost. 1999;  81 (3) 349-352
    PubMedGoogle Scholar
  • 38 Higgins J R, Kaiser T, Moses E K, North R, Brennecke S P. Prothrombin G20210A mutation: is it associated with pre-eclampsia?.  Gynecol Obstet Invest. 2000;  50 (4) 254-257
    CrossrefPubMedGoogle Scholar
  • 39 Sohda S, Arinami T, Hamada H, Yamada N, Hamaguchi H, Kubo T. Methylenetetrahydrofolate reductase polymorphism and pre-eclampsia.  J Med Genet. 1997;  34 (6) 525-526
    CrossrefPubMedGoogle Scholar
  • 40 Williams M A, Sanchez S E, Zhang C, Bazul V. Methylenetetrahydrofolate reductase 677 C—>T polymorphism and plasma folate in relation to pre-eclampsia risk among Peruvian women.  J Matern Fetal Neonatal Med. 2004;  15 (5) 337-344
    CrossrefPubMedGoogle Scholar
  • 41 Laivuori H, Lahermo P, Ollikainen V et al.. Susceptibility loci for preeclampsia on chromosomes 2p25 and 9p13 in Finnish families.  Am J Hum Genet. 2003;  72 (1) 168-177
    CrossrefPubMedGoogle Scholar
  • 42 Lin J, August P. Genetic thrombophilias and preeclampsia: a meta-analysis.  Obstet Gynecol. 2005;  105 (1) 182-192
    CrossrefPubMedGoogle Scholar
  • 43 Kosmas I P, Tatsioni A, Ioannidis J PA. Association of Leiden mutation in factor V gene with hypertension in pregnancy and pre-eclampsia: a meta-analysis.  J Hypertens. 2003;  21 (7) 1221-1228
    CrossrefPubMedGoogle Scholar
  • 44 Dudding T E, Attia J. The association between adverse pregnancy outcomes and maternal factor V Leiden genotype: a meta-analysis.  Thromb Haemost. 2004;  91 (4) 700-711
    PubMedGoogle Scholar
  • 45 GOPEC Consortium . Disentangling fetal and maternal susceptibility for pre-eclampsia: a British multicenter candidate-gene study.  Am J Hum Genet. 2005;  77 (1) 127-131
    CrossrefPubMedGoogle Scholar
  • 46 Nejatizadeh A, Stobdan T, Malhotra N, Pasha M A. The genetic aspects of pre-eclampsia: achievements and limitations.  Biochem Genet. 2008;  46 (7-8) 451-479
    CrossrefPubMedGoogle Scholar
  • 47 Sprengers E D, Kluft C. Plasminogen activator inhibitors.  Blood. 1987;  69 (2) 381-387
    PubMedGoogle Scholar
  • 48 Carrel R W, Boswell D R. Serpins: the superfamily of plasma serine proteinase inhibitors. In: Barrett A J, Salvesen G, eds. Proteinase Inhibitors. Amsterdam, The Netherlands: Elsevier Science; 1986: 403-420
    Google Scholar
  • 49 Gils A, Declerck P J. Structure-function relationships in serpins: current concepts and controversies.  Thromb Haemost. 1998;  80 (4) 531-541
    PubMedGoogle Scholar
  • 50 Laskowski Jr M, Kato I. Protein inhibitors of proteinases.  Annu Rev Biochem. 1980;  49 593-626
    CrossrefPubMedGoogle Scholar
  • 51 Pannekoek H, Veerman H, Lambers H et al.. Endothelial plasminogen activator inhibitor (PAI): a new member of the Serpin gene family.  EMBO J. 1986;  5 (10) 2539-2544
    PubMedGoogle Scholar
  • 52 Loskutoff D J, van Mourik J A, Erickson L A, Lawrence D. Detection of an unusually stable fibrinolytic inhibitor produced by bovine endothelial cells.  Proc Natl Acad Sci U S A. 1983;  80 (10) 2956-2960
    CrossrefPubMedGoogle Scholar
  • 53 Coleman P L, Barouski P A, Gelehrter T D. The dexamethasone-induced inhibitor of fibrinolytic activity in hepatoma cells. A cellular product which specifically inhibits plasminogen activation.  J Biol Chem. 1982;  257 (8) 4260-4264
    PubMedGoogle Scholar
  • 54 Kruithof E K, Tran-Thang C, Ransijn A, Bachmann F. Demonstration of a fast-acting inhibitor of plasminogen activators in human plasma.  Blood. 1984;  64 (4) 907-913
    PubMedGoogle Scholar
  • 55 Erickson L A, Ginsberg M H, Loskutoff D J. Detection and partial characterization of an inhibitor of plasminogen activator in human platelets.  J Clin Invest. 1984;  74 (4) 1465-1472
    CrossrefPubMedGoogle Scholar
  • 56 Nordenhem A, Wiman B. Plasminogen activator inhibitor-1 (PAI-1) content in platelets from healthy individuals genotyped for the 4G/5G polymorphism in the PAI-1 gene.  Scand J Clin Lab Invest. 1997;  57 (5) 453-461
    CrossrefPubMedGoogle Scholar
  • 57 Hekman C M, Loskutoff D J. Endothelial cells produce a latent inhibitor of plasminogen activators that can be activated by denaturants.  J Biol Chem. 1985;  260 (21) 11581-11587
    PubMedGoogle Scholar
  • 58 Angleton P, Chandler W L, Schmer G. Diurnal variation of tissue-type plasminogen activator and its rapid inhibitor (PAI-1).  Circulation. 1989;  79 (1) 101-106
    CrossrefPubMedGoogle Scholar
  • 59 Loskutoff D J, Linders M, Keijer J, Veerman H, van Heerikhuizen H, Pannekoek H. Structure of the human plasminogen activator inhibitor 1 gene: nonrandom distribution of introns.  Biochemistry. 1987;  26 (13) 3763-3768
    CrossrefPubMedGoogle Scholar
  • 60 Grenett H E, Wolkowicz P E, Benza R L, Tresnak J K, Wheeler C G, Booyse F M. Identification of a 251-bp fragment of the PAI-1 gene promoter that mediates the ethanol-induced suppression of PAI-1 expression.  Alcohol Clin Exp Res. 2001;  25 (5) 629-636
    CrossrefPubMedGoogle Scholar
  • 61 Asselbergs F W, Pattin K, Snieder H, Hillege H L, van Gilst W H, Moore J H. Genetic architecture of tissue-type plasminogen activator and plasminogen activator inhibitor-1.  Semin Thromb Hemost. 2008;  34 (6) 562-568
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 62 Reich D E, Cargill M, Bolk S et al.. Linkage disequilibrium in the human genome.  Nature. 2001;  411 (6834) 199-204
    CrossrefPubMedGoogle Scholar
  • 63 Patil N, Berno A J, Hinds D A et al.. Blocks of limited haplotype diversity revealed by high-resolution scanning of human chromosome 21.  Science. 2001;  294 (5547) 1719-1723
    CrossrefPubMedGoogle Scholar
  • 64 Kathiresan S, Gabriel S B, Yang Q et al.. Comprehensive survey of common genetic variation at the plasminogen activator inhibitor-1 locus and relations to circulating plasminogen activator inhibitor-1 levels.  Circulation. 2005;  112 (12) 1728-1735
    CrossrefPubMedGoogle Scholar
  • 65 Morange P E, Saut N, Alessi M C et al.. Association of plasminogen activator inhibitor (PAI)-1 (SERPINE1) SNPs with myocardial infarction, plasma PAI-1, and metabolic parameters: the HIFMECH study.  Arterioscler Thromb Vasc Biol. 2007;  27 (10) 2250-2257
    CrossrefPubMedGoogle Scholar
  • 66 Ye S, Green F R, Scarabin P Y et al.. The 4G/5G genetic polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene is associated with differences in plasma PAI-1 activity but not with risk of myocardial infarction in the ECTIM study. Etude CasTemoins de I'nfarctus du Mycocarde.  Thromb Haemost. 1995;  74 (3) 837-841
    PubMedGoogle Scholar
  • 67 Margaglione M, Cappucci G, d'Addedda M et al.. PAI-1 plasma levels in a general population without clinical evidence of atherosclerosis: relation to environmental and genetic determinants.  Arterioscler Thromb Vasc Biol. 1998;  18 (4) 562-567
    CrossrefPubMedGoogle Scholar
  • 68 Eriksson P, Kallin B, van 't Hooft F M, Båvenholm P, Hamsten A. Allele-specific increase in basal transcription of the plasminogen-activator inhibitor 1 gene is associated with myocardial infarction.  Proc Natl Acad Sci U S A. 1995;  92 (6) 1851-1855
    CrossrefPubMedGoogle Scholar
  • 69 Grubic N, Stegnar M, Peternel P, Kaider A, Binder B R. A novel G/A and the 4G/5G polymorphism within the promoter of the plasminogen activator inhibitor-1 gene in patients with deep vein thrombosis.  Thromb Res. 1996;  84 (6) 431-443
    CrossrefPubMedGoogle Scholar
  • 70 Moore J H, Smolkin M E, Lamb J M, Brown N J, Vaughan D E. The relationship between plasma t-PA and PAI-1 levels is dependent on epistatic effects of the ACE I/D and PAI-1 4G/5G polymorphisms.  Clin Genet. 2002;  62 (1) 53-59
    CrossrefPubMedGoogle Scholar
  • 71 Asselbergs F W, Williams S M, Hebert P R et al.. Epistatic effects of polymorphisms in genes from the renin-angiotensin, bradykinin, and fibrinolytic systems on plasma t-PA and PAI-1 levels.  Genomics. 2007;  89 (3) 362-369
    CrossrefPubMedGoogle Scholar
  • 72 Pérez-Martínez P, Adarraga-Cansino M D, Fernández de la Puebla R A et al.. The -675 4G/5G polymorphism at the Plasminogen Activator Inhibitor 1 (PAI-1) gene modulates plasma Plasminogen Activator Inhibitor 1 concentrations in response to dietary fat consumption.  Br J Nutr. 2008;  99 (4) 699-702
    PubMedGoogle Scholar
  • 73 Gohil R, Peck G, Sharma P. The genetics of venous thromboembolism. A meta-analysis involving approximately 120,000 cases and 180,000 controls.  Thromb Haemost. 2009;  102 (2) 360-370
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 74 Ye Z, Liu E H, Higgins J P et al.. Seven haemostatic gene polymorphisms in coronary disease: meta-analysis of 66,155 cases and 91,307 controls.  Lancet. 2006;  367 (9511) 651-658
    CrossrefPubMedGoogle Scholar
  • 75 Hermans P WM, Hibberd M L, Booy R Meningococcal Research Group et al. 4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene and outcome of meningococcal disease.  Lancet. 1999;  354 (9178) 556-560
    CrossrefPubMedGoogle Scholar
  • 76 Rossaak J I, Van Rij A M, Jones G T, Harris E L. Association of the 4G/5G polymorphism in the promoter region of plasminogen activator inhibitor-1 with abdominal aortic aneurysms.  J Vasc Surg. 2000;  31 (5) 1026-1032
    CrossrefPubMedGoogle Scholar
  • 77 Lin S, Huiya Z, Bo L, Wei W, Yongmei G. The plasminogen activator inhibitor-1 (PAI-1) gene -844 A/G and -675 4G/5G promoter polymorphism significantly influences plasma PAI-1 levels in women with polycystic ovary syndrome.  Endocrine. 2009;  36 (3) 503-509
    CrossrefPubMedGoogle Scholar
  • 78 Ma Z, Paek D, Oh C K. Plasminogen activator inhibitor-1 and asthma: role in the pathogenesis and molecular regulation.  Clin Exp Allergy. 2009;  39 (8) 1136-1144
    CrossrefPubMedGoogle Scholar
  • 79 Försti A, Lei H, Tavelin B et al.. Polymorphisms in the genes of the urokinase plasminogen activation system in relation to colorectal cancer.  Ann Oncol. 2007;  18 (12) 1990-1994
    CrossrefPubMedGoogle Scholar
  • 80 Minisini A M, Fabbro D, Di Loreto C et al.. Markers of the uPA system and common prognostic factors in breast cancer.  Am J Clin Pathol. 2007;  128 (1) 112-117
    CrossrefPubMedGoogle Scholar
  • 81 Lykke J A, Langhoff-Roos J, Young B, Paidas M J. Population-based investigations to study the association of cardiovascular polymorphisms and adverse pregnancy outcome.  Semin Perinatol. 2007;  31 (4) 219-222
    CrossrefPubMedGoogle Scholar
  • 82 Estellés A, Gilabert J, Keeton M et al.. Altered expression of plasminogen activator inhibitor type 1 in placentas from pregnant women with preeclampsia and/or intrauterine fetal growth retardation.  Blood. 1994;  84 (1) 143-150
    PubMedGoogle Scholar
  • 83 Estellés A, Gilabert J, Grancha S et al.. Abnormal expression of type 1 plasminogen activator inhibitor and tissue factor in severe preeclampsia.  Thromb Haemost. 1998;  79 (3) 500-508
    PubMedGoogle Scholar
  • 84 Yamada N, Arinami T, Yamakawa-Kobayashi K et al.. The 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene is associated with severe preeclampsia.  J Hum Genet. 2000;  45 (3) 138-141
    CrossrefPubMedGoogle Scholar
  • 85 Glueck C J, Kupferminc M J, Fontaine R N, Wang P, Weksler B B, Eldor A. Genetic hypofibrinolysis in complicated pregnancies.  Obstet Gynecol. 2001;  97 (1) 44-48
    CrossrefPubMedGoogle Scholar
  • 86 Fabbro D, D'Elia A V, Spizzo R et al.. Association between plasminogen activator inhibitor 1 gene polymorphisms and preeclampsia.  Gynecol Obstet Invest. 2003;  56 (1) 17-22
    CrossrefPubMedGoogle Scholar
  • 87 Morrison E R, Miedzybrodzka Z H, Campbell D M et al.. Prothrombotic genotypes are not associated with pre-eclampsia and gestational hypertension: results from a large population-based study and systematic review.  Thromb Haemost. 2002;  87 (5) 779-785
    PubMedGoogle Scholar
  • 88 Pegoraro R J, Hira B, Rom L, Moodley J. Plasminogen activator inhibitor type 1 (PAI1) and platelet glycoprotein IIIa (PGIIIa) polymorphisms in black South Africans with pre-eclampsia.  Acta Obstet Gynecol Scand. 2003;  82 (4) 313-317
    CrossrefPubMedGoogle Scholar
  • 89 Häkli T, Romppanen E L, Hiltunen M, Helisalmi S, Punnonen K, Heinonen S. Plasminogen activator inhibitor-1 polymorphism in women with pre-eclampsia.  Genet Test. 2003;  7 (3) 265-268
    CrossrefPubMedGoogle Scholar
  • 90 Gerhardt A, Goecke T W, Beckmann M W et al.. 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. 2005;  3 (4) 686-691
    CrossrefPubMedGoogle Scholar
  • 91 De Maat M P, Jansen M W, Hille E T et al.. Preeclampsia and its interaction with common variants in thrombophilia genes.  J Thromb Haemost. 2004;  2 (9) 1588-1593
    CrossrefPubMedGoogle Scholar
  • 92 Tempfer C B, Jirecek S, Riener E K et al.. Polymorphisms of thrombophilic and vasoactive genes and severe preeclampsia: a pilot study.  J Soc Gynecol Investig. 2004;  11 (4) 227-231
    CrossrefPubMedGoogle Scholar
  • 93 Kobashi G. Genetic and environmental factors associated with the development of hypertension in pregnancy.  J Epidemiol. 2006;  16 (1) 1-8
    CrossrefPubMedGoogle Scholar
  • 94 Dalmáz C A, Santos K G, Botton M R, Tedoldi C L, Roisenberg I. Relationship between polymorphisms in thrombophilic genes and preeclampsia in a Brazilian population.  Blood Cells Mol Dis. 2006;  37 (2) 107-110
    CrossrefPubMedGoogle Scholar
  • 95 Wiwanitkit V. Correlation between plasminogen activator inhibitor-1 4G/5G polymorphism and pre-eclampsia: an appraisal.  Arch Gynecol Obstet. 2006;  273 (6) 322-324
    CrossrefPubMedGoogle Scholar

Professor Giuseppe DamanteM.D. Ph.D. 

Dipartimento di Scienze e Tecnologie Biomediche

Università di Udine, Piazzale Kolbe 1, 33100 Udine, Italy

eMail: giuseppe.damante@uniud.it