The N125S polymorphism in the cathepsin G gene (rs45567233) is associated with susceptibility to osteomyelitis in a Spanish population


Autoři: Laura Pérez-Is aff001;  Marcos G. Ocaña aff003;  A. Hugo Montes aff001;  José A. Carton aff002;  Victoria Álvarez aff005;  Álvaro Meana aff006;  Joshua Fierer aff007;  Eulalia Valle-Garay aff001;  Víctor Asensi aff002
Působiště autorů: Biochemistry and Molecular Biology, University Medical School, Oviedo, Spain aff001;  Group of Translational Research in Infectious Diseases, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain aff002;  Biotechnological and Biomedical Assays Unit, University Medical School Oviedo, Spain aff003;  Infectious Diseases, Hospital Universitario Central de Asturias, University Medical School, Oviedo, Spain aff004;  Molecular Genetics Unit-Nephrology Research Institute, Hospital Universitario Central de Asturias, Oviedo, Spain aff005;  Community Center for Blood and Tissues of Asturias, CIBERER U714, Oviedo, Spain aff006;  Infectious Diseases Section, VAMC and University of California, San Diego, California, United States of America aff007
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0220022

Souhrn

Background

Osteomyelitis is a bone infection, most often caused by Staphylococcus aureus, in which neutrophils play a key role. Cathepsin G (CTSG) is a bactericidal serine protease stored in the neutrophil azurophilic granules. CTSG regulates inflammation, activating matrix metalloproteinases (MMPs), and coagulation. Lactoferrin (LF), a neutrophil glycoprotein, increases CTSG catalytic activity and induces inflammation. The aim of this study was to analyze a potential association between a CTSG gene polymorphism (Asn125Ser or N125S, rs45567233), that modifies CTSG activity, and could affect susceptibility to, or outcome of, bacterial osteomyelitis.

Methods

CTSG N125S polymorphism was genotyped in 329 osteomyelitis patients and 415 controls), Blood coagulation parameters, serum CTSG activity, LF, MMP-1, MMP-13, and soluble receptor activator for nuclear factor κ B ligand (sRANKL) levels were assessed in carriers of the different CTSG genotypes.

Results

CTSG N125S (AG) genotype was significantly more frequent among osteomyelitis patients than controls (15.5% vs. 9.4%, p = 0.014). CTSG N125S variant G allele (AG +GG) was also more frequent among osteomyelitis patients (8.1% vs. 4.7%, p = 0.01). Serum CTSG activity and LF levels were significantly higher in osteomyelitis patients carrying the G allele compared to those with the AA genotype, (p<0.04). Serum MMP-1 was lower in the G allele carriers (p = 0.01). There was no association between these genotypes and clinical characteristics of osteomyelitis, or coagulation parameters, MMP-13, and sRANKL serum levels.

Conclusions

Differences in the CTSG gene might enhance osteomyelitis susceptibility by increasing CTSG activity and LF levels.

Klíčová slova:

Alleles – Heredity – Inflammation – Inflammatory diseases – Neutrophils – Osteomyelitis – Staphylococcal infection – Variant genotypes


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