title: The 4G/5G polymorphism of the type 1 plasminogen activator inhibitor gene and thrombosis in patients with antiphospholipid syndrome.
abstract: OBJECTIVE
  To investigate the relationship between the 4G/5G polymorphism of the type 1 plasminogen activator inhibitor (PAI-1) gene and thrombotic manifestations in patients with antiphospholipid syndrome (APS).
  
  
  METHODS
  We studied a total of 247 patients included in the following 4 groups: 70 patients with primary APS, 104 patients with systemic lupus erythematosus (40 with antiphospholipid antibodies [aPL] and clinical [secondary] APS, 13 with aPL but without clinical APS, and 51 with neither detectable aPL nor a history of thrombosis), 14 asymptomatic individuals with aPL, and 59 patients with thrombosis but without known thrombosis risk factors. A control group of 100 healthy individuals was also analyzed. PAI-1 4G/5G polymorphism was determined by polymerase chain reaction and endonuclease digestion.
  
  
  RESULTS
  The allele frequency of 4G/5G in controls was 0.47/0.53. There were no differences in allele distribution among patient groups or between patients and controls. However, a higher frequency of the 4G allele was observed in APS patients with versus those without thrombosis (0.57 versus 0.39; P < 0.05) (odds ratio [OR] 2.83, 95% confidence interval [95% CI] 1.18-6.76). This higher frequency of the 4G allele was attributable to the higher frequency in patients with versus those without arterial thrombosis (0.64 versus 0.43; P < 0.01) (OR 5.96, 95% CI 1.67-21.32), while patients with venous thrombosis had an allele distribution similar to that of those without venous thrombosis (0.49 versus 0.50; P not significant). There was a trend toward higher PAI-1 antigen and activity levels in APS patients and controls with the 4G/4G genotype, but this did not reach statistical significance.
  
  
  CONCLUSIONS
  The presence of the 4G allele of the 4G/5G polymorphism of the PAI-1 gene may be an additional risk factor for the development of arterial thrombosis in APS.
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, Barcelona, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Tàssies
authors.forename: G
authors.initials: G
authors.lastname: Espinosa
authors.forename: F J
authors.initials: FJ
authors.lastname: Muñoz-Rodríguez
authors.forename: C
authors.initials: C
authors.lastname: Freire
authors.forename: R
authors.initials: R
authors.lastname: Cervera
authors.forename: J
authors.initials: J
authors.lastname: Monteagudo
authors.forename: S
authors.initials: S
authors.lastname: Maragall
authors.forename: G
authors.initials: G
authors.lastname: Escolar
authors.forename: M
authors.initials: M
authors.lastname: Ingelmo
authors.forename: A
authors.initials: A
authors.lastname: Ordinas
authors.forename: J
authors.initials: J
authors.lastname: Font
authors.forename: J C
authors.initials: JC
authors.lastname: Reverter
mesh_terms: D000328:Adult; D016736:Antiphospholipid Syndrome / Q000150:complications* / Q000235:genetics; D001157:Arterial Occlusive Diseases / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D016207:Cytokines / Q000097:blood; D005260:Female; D005342:Fibrinolysis / Q000235:genetics; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D020246:Venous Thrombosis / Q000209:etiology* / Q000235:genetics
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; D014409:Tumor Necrosis Factor-alpha