Investigation of TLR2 and TLR4 Polymorphisms and Sepsis Susceptibility: Computational and Experimental Approaches
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 <i&...
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MDPI AG
2022-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/18/10982 |
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| author | Mohammed Y. Behairy Ali A. Abdelrahman Eman A. Toraih Emad El-Deen A. Ibrahim Marwa M. Azab Anwar A. Sayed Hany R. Hashem |
| author_facet | Mohammed Y. Behairy Ali A. Abdelrahman Eman A. Toraih Emad El-Deen A. Ibrahim Marwa M. Azab Anwar A. Sayed Hany R. Hashem |
| author_sort | Mohammed Y. Behairy |
| collection | DOAJ |
| description | 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 <i>TLR2</i> and <i>TLR4</i> 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 <i>TLR2</i> Arg753Gln polymorphisms and sepsis under the over-dominant model (<i>p</i> = 0.043). In contrast, we did not find a significant difference with the <i>TLR4</i> Asp299Gly polymorphism with sepsis. However, there was a significant association between <i>TLR4</i> Asp299Gly polymorphisms and <i>Acinetobacter baumannii</i> infection which is quite a virulent organism in ICU (<i>p</i> = 0.001) and post-surgical cohorts (<i>p</i> = 0.033). Our results conclude that the <i>TLR2</i> genotype may be a risk factor for sepsis in adult patients. |
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| format | Article |
| id | doaj.art-0cbacb02ce52488f89c2f4e174ca1a79 |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:40:32Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0cbacb02ce52488f89c2f4e174ca1a792023-11-23T16:51:38ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123181098210.3390/ijms231810982Investigation of TLR2 and TLR4 Polymorphisms and Sepsis Susceptibility: Computational and Experimental ApproachesMohammed Y. Behairy0Ali A. Abdelrahman1Eman A. Toraih2Emad El-Deen A. Ibrahim3Marwa M. Azab4Anwar A. Sayed5Hany R. Hashem6Department of Microbiology and Immunology, Faculty of Pharmacy, University of Sadat City, Sadat City 32958, EgyptDepartment of Microbiology and Immunology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, EgyptDepartment of Surgery, School of Medicine, Tulane University, New Orleans, LA 70112, USADepartment of Anesthesia, Intensive Care and Pain Management, Faculty of Medicine, Suez Canal University, Ismailia 41522, EgyptDepartment of Microbiology and Immunology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, EgyptDepartment of Medical Microbiology and Immunology, Taibah University, Madinah 42353, Saudi ArabiaDepartment of Microbiology and Immunology, Faculty of Pharmacy, Fayoum University, Fayoum 63514, EgyptToll-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 <i>TLR2</i> and <i>TLR4</i> 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 <i>TLR2</i> Arg753Gln polymorphisms and sepsis under the over-dominant model (<i>p</i> = 0.043). In contrast, we did not find a significant difference with the <i>TLR4</i> Asp299Gly polymorphism with sepsis. However, there was a significant association between <i>TLR4</i> Asp299Gly polymorphisms and <i>Acinetobacter baumannii</i> infection which is quite a virulent organism in ICU (<i>p</i> = 0.001) and post-surgical cohorts (<i>p</i> = 0.033). Our results conclude that the <i>TLR2</i> genotype may be a risk factor for sepsis in adult patients.https://www.mdpi.com/1422-0067/23/18/10982TLRpolymorphisminfectionsepsisseptic shock |
| spellingShingle | Mohammed Y. Behairy Ali A. Abdelrahman Eman A. Toraih Emad El-Deen A. Ibrahim Marwa M. Azab Anwar A. Sayed Hany R. Hashem Investigation of TLR2 and TLR4 Polymorphisms and Sepsis Susceptibility: Computational and Experimental Approaches International Journal of Molecular Sciences TLR polymorphism infection sepsis septic shock |
| title | Investigation of TLR2 and TLR4 Polymorphisms and Sepsis Susceptibility: Computational and Experimental Approaches |
| title_full | Investigation of TLR2 and TLR4 Polymorphisms and Sepsis Susceptibility: Computational and Experimental Approaches |
| title_fullStr | Investigation of TLR2 and TLR4 Polymorphisms and Sepsis Susceptibility: Computational and Experimental Approaches |
| title_full_unstemmed | Investigation of TLR2 and TLR4 Polymorphisms and Sepsis Susceptibility: Computational and Experimental Approaches |
| title_short | Investigation of TLR2 and TLR4 Polymorphisms and Sepsis Susceptibility: Computational and Experimental Approaches |
| title_sort | investigation of tlr2 and tlr4 polymorphisms and sepsis susceptibility computational and experimental approaches |
| topic | TLR polymorphism infection sepsis septic shock |
| url | https://www.mdpi.com/1422-0067/23/18/10982 |
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