{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T05:32:24Z","timestamp":1779168744711,"version":"3.51.4"},"reference-count":59,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T00:00:00Z","timestamp":1644364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["RF-2011-02348364"],"award-info":[{"award-number":["RF-2011-02348364"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Many causal mechanisms in sepsis susceptibility are largely unknown and the functional genetic polymorphisms (GP) of matrix metalloproteinases (MMPs) and their natural tissue inhibitor of MMPs (TIMP1) could play a role in its development. GPs of MMPs and TIMP (namely MMP-1 rs1799750, MMP-3 rs3025058, MMP-8 rs11225395, MMP-9 rs2234681, and TIMP-1 rs4898) have been compared in 1058 patients with suspected sepsis to assess the association with susceptibility and etiology of sepsis. Prevalence of MMP8 rs11225395 G\/G genotype was higher in sepsis patients than in those with non-infective Systemic Inflammatory Reaction Syndrome (35.6 vs. 26%, hazard ratio, HR 1.56, 95% C.I. 1.04\u20132.42, p = 0.032). G\/G patients developed less hyperthermia (p = 0.041), even after stratification for disease severity (p = 0.003). Patients carrying the 6A allele in MMP3 rs3025058 had a higher probability of microbiologically-proven sepsis (HR 1.4. 95%C.I. 1.01\u20131.94, p = 0.044), particularly when due to virus (H.R. 2.14, 95% C.I. 1.06\u20134.31, p = 0.046), while MMP-1 G\/G genotype patients carried a higher risk for intracellular bacteria (Chlamydia, Mycoplasma, and Legionella, H.R. 6.46, 95% C.I. 1.58\u201326.41, p = 0.003). Neither severity of sepsis at presentation, nor 30-day mortality were influenced by the investigated variants or their haplotype. MMP8 rs11225395 G\/G carriers have lower temperature at presentation and a more than 50% increased susceptibility to sepsis. Among patients with sepsis, carriers of MMP1 rs1799750 G\/G have an increased susceptibility for intracellular pathogen infections, while virus serology is more often positive in those with the MMP3 rs3025058 A\/A genotype.<\/jats:p>","DOI":"10.3390\/biom12020279","type":"journal-article","created":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T21:19:06Z","timestamp":1644441546000},"page":"279","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Genetic Variants of Matrix Metalloproteinase and Sepsis: The Need Speed Study"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8918-7622","authenticated-orcid":false,"given":"Nicola","family":"Fiotti","sequence":"first","affiliation":[{"name":"Unit of Internal Medicine, Department of Medical Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5862-9077","authenticated-orcid":false,"given":"Filippo","family":"Mearelli","sequence":"additional","affiliation":[{"name":"Unit of Internal Medicine, Department of Medical Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filippo Giorgio","family":"Di Girolamo","sequence":"additional","affiliation":[{"name":"Unit of Internal Medicine, Department of Medical Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy"},{"name":"SC Assistenza Farmaceutica, Cattinara Hospital, Azienda Sanitaria Universitaria Integrata di Trieste, 34149 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8248-1976","authenticated-orcid":false,"given":"Luigi Mario","family":"Castello","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, Internal Medicine, A.O. \u201cSanti Antonio e Biagio e Cesare Arrigo\u201d, 15121 Alessandria, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessio","family":"Nunnari","sequence":"additional","affiliation":[{"name":"Unit of Internal Medicine, Department of Medical Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Di Somma","sequence":"additional","affiliation":[{"name":"Unit of Emergency Medicine, Department of Medical Surgery Sciences and Translational Medicine, University \u201cSapienza\u201d of Rome, 00185 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2719-1217","authenticated-orcid":false,"given":"Enrico","family":"Lupia","sequence":"additional","affiliation":[{"name":"Unit of Emergency Medicine, Department of Medical Sciences, University of Turin, 10124 Torino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3942-4604","authenticated-orcid":false,"given":"Efrem","family":"Colonetti","sequence":"additional","affiliation":[{"name":"Unit of Internal Medicine, Department of Clinical and Experimental Sciences, University of Brescia, 25121 Brescia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Lorenza","family":"Muiesan","sequence":"additional","affiliation":[{"name":"Unit of Internal Medicine, Department of Clinical and Experimental Sciences, University of Brescia, 25121 Brescia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Montrucchio","sequence":"additional","affiliation":[{"name":"Unit of Emergency Medicine, Department of Medical Sciences, University of Turin, 10124 Torino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Giansante","sequence":"additional","affiliation":[{"name":"Unit of Internal Medicine, Department of Medical Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gian Carlo","family":"Avanzi","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6397-1598","authenticated-orcid":false,"given":"Gianni","family":"Biolo","sequence":"additional","affiliation":[{"name":"Unit of Internal Medicine, Department of Medical Surgical and Health Sciences, University of Trieste, 34149 Trieste, 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