Journal Article

tPA Alu (I/D) Polymorphism Associates With Bacterial Osteomyelitis

Eulalia Valle-Garay, Angel H. Montes, Jose R. Corte, Alvaro Meana, Joshua Fierer and Victor Asensi

in The Journal of Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 208, issue 2, pages 218-223
Published in print July 2013 | ISSN: 0022-1899
Published online April 2013 | e-ISSN: 1537-6613 | DOI: https://dx.doi.org/10.1093/infdis/jit158
tPA Alu (I/D) Polymorphism Associates With Bacterial Osteomyelitis

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

Journal Article.  3275 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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