{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:05Z","timestamp":1787028485565,"version":"build-2736575974"},"reference-count":53,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T00:00:00Z","timestamp":1663545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Toll-like receptors (TLR) play an eminent role in the regulation of immune responses to invading pathogens during sepsis. TLR genetic variants might influence individual susceptibility to developing sepsis. The current study aimed to investigate the association of genetic polymorphisms of the TLR2 and TLR4 with the risk of developing sepsis with both a pilot study and in silico tools. Different in silico tools were used to predict the impact of our SNPs on protein structure, stability, and function. Furthermore, in our prospective study, all patients matching the inclusion criteria in the intensive care units (ICU) were included and followed up, and DNA samples were genotyped using real-time polymerase chain reaction (RT-PCR) technology. There was a significant association between TLR2 Arg753Gln polymorphisms and sepsis under the over-dominant model (p = 0.043). In contrast, we did not find a significant difference with the TLR4 Asp299Gly polymorphism with sepsis. However, there was a significant association between TLR4 Asp299Gly polymorphisms and Acinetobacter baumannii infection which is quite a virulent organism in ICU (p = 0.001) and post-surgical cohorts (p = 0.033). Our results conclude that the TLR2 genotype may be a risk factor for sepsis in adult patients.<\/jats:p>","DOI":"10.3390\/ijms231810982","type":"journal-article","created":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T21:47:27Z","timestamp":1663624047000},"page":"10982","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Investigation of TLR2 and TLR4 Polymorphisms and Sepsis Susceptibility: Computational and Experimental Approaches"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8415-2914","authenticated-orcid":false,"given":"Mohammed Y.","family":"Behairy","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, University of Sadat City, Sadat City 32958, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali A.","family":"Abdelrahman","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9267-3787","authenticated-orcid":false,"given":"Eman A.","family":"Toraih","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Medicine, Tulane University, New Orleans, LA 70112, USA"},{"name":"Genetics Unit, Department of Histology & Cell Biology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emad El-Deen A.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Intensive Care and Pain Management, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa M.","family":"Azab","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2243-0971","authenticated-orcid":false,"given":"Anwar A.","family":"Sayed","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Taibah University, Madinah 42353, Saudi Arabia"},{"name":"Department of Surgery and Cancer, Imperial College London, London SW7 2BX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hany R.","family":"Hashem","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Fayoum University, Fayoum 63514, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2226","DOI":"10.1016\/S0140-6736(03)13779-8","article-title":"Where and why are 10 million children dying every year?","volume":"361","author":"Black","year":"2003","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1001\/jama.2009.1754","article-title":"International study of the prevalence and outcomes of infection in intensive care units","volume":"302","author":"Vincent","year":"2009","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1177\/0300060513504358","article-title":"Polymorphisms of the toll-like receptor 2 and 4 genes are associated with faster progression and a more severe course of sepsis in critically ill patients","volume":"42","author":"Nachtigall","year":"2014","journal-title":"J. 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