tPA Alu (I/D) polymorphism associates with bacterial osteomyelitis

J Infect Dis. 2013 Jul 15;208(2):218-23. doi: 10.1093/infdis/jit158. Epub 2013 Apr 9.


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.

Patients and 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.

Keywords: PAI-1; fibrinolysis; osteomyelitis; polymorphisms; tPA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Female
  • Fibrinolysis / genetics
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Homozygote
  • Humans
  • Male
  • Middle Aged
  • Osteomyelitis / blood
  • Osteomyelitis / genetics*
  • Osteomyelitis / microbiology
  • Polymorphism, Genetic
  • Tissue Plasminogen Activator / genetics*
  • Young Adult


  • Tissue Plasminogen Activator