title: tPA Alu (I/D) polymorphism associates with bacterial osteomyelitis.
abstract: BACKGROUND
  Coagulation and fibrinolysis are important in infections and systemic inflammatory response syndrome. Polymorphisms in plasminogen activator inhibitor-1 (PAI-1, SERPINE1) and tissue plasminogen activator (tPA, PLAT), such as PAI-1 (-675 4G/5G deletion/insertion) and tPA (Alu insertion/deletion [I/D]), are associated with strokes, myocardial infarctions, bacterial infections and septic shock severity, and trauma. Osteomyelitis is a mostly posttraumatic, Staphylococcal bone infection.
  
  
  METHODS
  tPA Alu (I/D) (rs4646972) and PAI-1 (4G/5G) (rs1799889) polymorphisms were studied by DNA amplification with polymerase chain reaction in 261 patients with osteomyelitis and in 299 matched blood donors. Plasma PAI-1/tPA complex was assessed by enzyme-linked immuosorbent assay.
  
  
  RESULTS
  II homozygotes (37.9% vs 19.1%) and I allele carriers (56.3% vs 46.3%) for the tPA Alu (I/D) polymorphism were significantly more frequent in osteomyelitis patients compared to controls (P < .001). II genotype carrier osteomyelitis patients had lower PAI-1/tPA complex levels compared to those with the D allele (P ≤ .04). There was no association between these genotypes and chronicity of osteomyelitis, post-traumatic etiology, or with a specific bacterial etiology. PAI-1 (4G/4G) homozygotes were not significantly different between osteomyelitis patients and controls (P = .1).
  
  
  CONCLUSIONS
  We report for the first time to our knowledge an association between the tPA Alu (I/D) polymorphism and susceptibility to bacterial osteomyelitis, perhaps by fibrinolysis dysfunction.
authors.affiliation: Biochemistry and Molecular Biology, Oviedo University School of Medicine and Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Eulalia
authors.initials: E
authors.lastname: Valle-Garay
authors.forename: Angel H
authors.initials: AH
authors.lastname: Montes
authors.forename: Jose R
authors.initials: JR
authors.lastname: Corte
authors.forename: Alvaro
authors.initials: A
authors.lastname: Meana
authors.forename: Joshua
authors.initials: J
authors.lastname: Fierer
authors.forename: Victor
authors.initials: V
authors.lastname: Asensi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D005260:Female; D005342:Fibrinolysis / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010019:Osteomyelitis / Q000097:blood / Q000235:genetics* / Q000382:microbiology; D011110:Polymorphism, Genetic; D010959:Tissue Plasminogen Activator / Q000235:genetics*; D055815:Young Adult
chemical_list: D010959:Tissue Plasminogen Activator
keywords: PAI-1; fibrinolysis; osteomyelitis; polymorphisms; tPA