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Published on: April 1, 2019
tPA Alu (I/D) polymorphism associates with bacterial osteomyelitis
Eulalia Valle-Garay1, Angel H Montes, Jose R Corte
1Biochemistry and Molecular Biology, Oviedo University School of Medicine and Hospital Universitario Central de Asturias, Oviedo, Spain.
The tissue plasminogen activator (tPA) Alu insertion/deletion polymorphism is linked to increased susceptibility to bacterial osteomyelitis. This genetic variation may impact fibrinolysis, a key process in infection control.
Area of Science:
- Genetics
- Infectious Diseases
- Hematology
Background:
- Coagulation and fibrinolysis are critical in managing infections and systemic inflammatory response syndrome.
- Genetic variations in plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) are linked to various vascular and infectious conditions.
- Osteomyelitis, a bone infection often caused by Staphylococcus, frequently follows trauma.
Purpose of the Study:
- To investigate the association between tPA Alu (I/D) and PAI-1 (4G/5G) polymorphisms and susceptibility to bacterial osteomyelitis.
- To explore the relationship between these genetic polymorphisms and plasma levels of the PAI-1/tPA complex.
Main Methods:
- Genotyping of tPA Alu (I/D) (rs4646972) and PAI-1 (4G/5G) (rs1799889) polymorphisms using polymerase chain reaction (PCR).
- Analysis of 261 osteomyelitis patients and 299 matched blood donors.
- Measurement of plasma PAI-1/tPA complex levels via enzyme-linked immunosorbent assay (ELISA).
Main Results:
- The tPA Alu (I/D) II genotype and I allele were significantly more prevalent in osteomyelitis patients compared to controls (P < .001).
- Osteomyelitis patients with the II genotype exhibited lower plasma PAI-1/tPA complex levels (P ≤ .04).
- No significant association was found between these polymorphisms and osteomyelitis chronicity, post-traumatic etiology, or specific bacterial causes. PAI-1 (4G/4G) homozygotes showed no significant difference between groups.
Conclusions:
- This study identifies, for the first time, an association between the tPA Alu (I/D) polymorphism and susceptibility to bacterial osteomyelitis.
- The findings suggest a potential role for fibrinolysis dysfunction in the pathogenesis of osteomyelitis related to this genetic variation.
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