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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 <jats:italic>TLR6<\/jats:italic> (P249S) was associated with significantly smaller lesions while homozygosity for the allelic variant <jats:italic>TLR1<\/jats:italic> (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 <jats:italic>TLR1<\/jats:italic> (S248N) had significantly larger lesions. Polymorphisms in <jats:italic>TLR1<\/jats:italic> and <jats:italic>TLR6<\/jats:italic> influence the severity of cSSSIs as assessed by the lesion size of major abscesses and DFIs. <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/clinicaltrial.gov\">ClinicalTrial.gov<\/jats:ext-link> Identifier: NCT 00402727<\/jats:p>","DOI":"10.1007\/s10096-019-03732-7","type":"journal-article","created":{"date-parts":[[2019,12,2]],"date-time":"2019-12-02T12:11:03Z","timestamp":1575288663000},"page":"353-360","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Lesion size is associated with genetic polymorphisms in TLR1, TLR6, and TIRAP genes in patients with major abscesses and diabetic foot infections"],"prefix":"10.1007","volume":"39","author":[{"given":"Valentino","family":"D\u2019Onofrio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annelie A.","family":"Monnier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Kremer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark H. 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