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Eur J Clin Microbiol Infect Dis. 2019 Nov 30. doi: 10.1007/s10096-019-03732-7. [Epub ahead of print]

Lesion size is associated with genetic polymorphisms in TLR1, TLR6, and TIRAP genes in patients with major abscesses and diabetic foot infections.

Author information

1
Faculty of Medicine and Life Sciences, Research Group of Immunology and Biochemistry, Hasselt University, Hasselt, Belgium.
2
Department of Infectious Diseases and Immunity, Jessa Hospital, Hasselt, Belgium.
3
Department of Internal Medicine and Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
4
Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Hasselt University, Hasselt, Belgium.
5
Department of Biosciences, Geoffrey Pope Building, University of Exeter, Stocker Road, Exeter, EX4 4QD, UK.
6
Human Genomics Laboratory, Craiova University of Medicine and Pharmacy, Craiova, Romania.
7
Faculty of Medicine and Life Sciences, Research Group of Immunology and Biochemistry, Hasselt University, Hasselt, Belgium. inge.gyssens@radboudumc.nl.
8
Department of Internal Medicine and Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands. inge.gyssens@radboudumc.nl.

Abstract

Genetic variation in Toll-like receptors (TLRs) has previously been associated with susceptibility to complicated skin and skin structure infections (cSSSIs). The aim of this study was to investigate associations between the severity of cSSSIs, i.e., major abscesses and diabetic foot infections (DFIs), and a set of genetic polymorphisms in the Toll-like receptor pathway. A total of 121 patients with major abscesses and 132 with DFIs participating in a randomized clinical trial were genotyped for 13 nonsynonymous single-nucleotide polymorphisms (SNPs) in genes coding for TLRs and the signaling adaptor molecule TIRAP. Infection severity was defined by lesion size at clinical presentation for both types of infections. The PEDIS infection score was also used to define severity of DFIs. Linear regression models were used to study factors independently associated with severity. In patients with large abscesses, hetero- or homozygosity for the allelic variant TLR6 (P249S) was associated with significantly smaller lesions while homozygosity for the allelic variant TLR1 (R80T) was associated with significantly larger lesions. PRRs genes were not significantly associated with PEDIS. However, patients with DFI hetero- or homozygous for the allelic variant TLR1 (S248N) had significantly larger lesions. Polymorphisms in TLR1 and TLR6 influence the severity of cSSSIs as assessed by the lesion size of major abscesses and DFIs. ClinicalTrial.gov Identifier: NCT00402727.

KEYWORDS:

Abscess; Diabetic foot infection; Innate immunity; Pattern recognition receptors; Single-nucleotide polymorphism

PMID:
31786695
DOI:
10.1007/s10096-019-03732-7

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