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

Abstract

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. 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. 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). 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.