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      Toll‐like receptor 4 polymorphisms in Saudi population with cardiovascular diseases

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          Abstract

          Background

          Toll‐like receptors play a substantial role in innate immunity and the effects of TLR4 genetic variants on cardiovascular diseases are still largely unknown. Therefore, we aimed to investigate the effects of TLR4 polymorphisms on cardiovascular diseases risk in the Saudi population.

          Methods

          Three tag single‐nucleotide polymorphisms (rs2770150, rs10759931, and rs4986790) in TLR4 were studied on 222 unrelated patients with cardiovascular diseases and 190 healthy volunteers.

          Results

          We found that, in patients over 60 years old, the frequency of the TT genotype in rs2770150 and the variant allele G in rs10759931 were higher compared to the control group. Based on gender, the genotype frequency of rs2770150 increases the risk for cardiovascular diseases in female patients by 3.6‐fold. The allele frequency for the G allele of rs10759931 increased the risk for CVDs in male patients by more than 1.5‐fold. Furthermore, the genotype frequency of rs2770150 had a significant association with cardiovascular diseases in patients without hypertension and G allele of rs10759931 significantly increased the risk of cardiovascular diseases in patients that smoked. After Bonferroni correction only patients without hypertension showed significant risk of CVD with rs2770150.

          Conclusion

          A deeper understanding of the genetic variability of TLR4 will enable us to better identification of biomarkers for early detection and prognosis, and also enhance the decision‐making process of treatments for cardiovascular diseases.

          Abstract

          The genotype frequency of rs2770150 had a significantly association with Cardio Vascular diseases in Saudi patients.

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          Most cited references60

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          LPS/TLR4 signal transduction pathway.

          The stimulation of Toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS) induces the release of critical proinflammatory cytokines that are necessary to activate potent immune responses. LPS/TLR4 signaling has been intensively studied in the past few years. Here we review molecules involved in TLR4-mediated signaling, including players that are involved in the negative regulation of this important pathway.
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            The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights

            Since the discovery of glucocorticoids in the 1940s and the recognition of their anti-inflammatory effects, they have been amongst the most widely used and effective treatments to control inflammatory and autoimmune diseases. However, their clinical efficacy is compromised by the metabolic effects of long-term treatment, which include osteoporosis, hypertension, dyslipidaemia and insulin resistance/type 2 diabetes mellitus. In recent years, a great deal of effort has been invested in identifying compounds that separate the beneficial anti-inflammatory effects from the adverse metabolic effects of glucocorticoids, with limited effect. It is clear that for these efforts to be effective, a greater understanding is required of the mechanisms by which glucocorticoids exert their anti-inflammatory and immunosuppressive actions. Recent research is shedding new light on some of these mechanisms and has produced some surprising new findings. Some of these recent developments are reviewed here.
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              Toll-like receptors in innate immunity.

              K Takeda (2004)
              Functional characterization of Toll-like receptors (TLRs) has established that innate immunity is a skillful system that detects invasion of microbial pathogens. Recognition of microbial components by TLRs initiates signal transduction pathways, which triggers expression of genes. These gene products control innate immune responses and further instruct development of antigen-specific acquired immunity. TLR signaling pathways are finely regulated by TIR domain-containing adaptors, such as MyD88, TIRAP/Mal, TRIF and TRAM. Differential utilization of these TIR domain-containing adaptors provides specificity of individual TLR-mediated signaling pathways. Several mechanisms have been elucidated that negatively control TLR signaling pathways, and thereby prevent overactivation of innate immunity leading to fatal immune disorders. The involvement of TLR-mediated pathways in autoimmune and inflammatory diseases has been proposed. Thus, TLR-mediated activation of innate immunity controls not only host defense against pathogens but also immune disorders.
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                Author and article information

                Contributors
                Abdelhabib.semlali@greb.ulaval.ca
                Journal
                Mol Genet Genomic Med
                Mol Genet Genomic Med
                10.1002/(ISSN)2324-9269
                MGG3
                Molecular Genetics & Genomic Medicine
                John Wiley and Sons Inc. (Hoboken )
                2324-9269
                21 July 2019
                September 2019
                : 7
                : 9 ( doiID: 10.1002/mgg3.v7.9 )
                : e852
                Affiliations
                [ 1 ] Groupe de Recherche en Écologie Buccale, Faculté de Médecine Dentaire Université Laval Québec QC Canada
                [ 2 ] Genome Research Chair, Department of Biochemistry College of Science King Saud University Riyadh Kingdom of Saudi Arabia
                [ 3 ] Zoology Department College of Science King Saud University Riyadh Kingdom of Saudi Arabia
                [ 4 ] National Center for Genomics Research (NCGR), King Abdulaziz City for Science and Technology Riyadh Saudi Arabia
                [ 5 ] Department of Biochemistry, Faculty of Science King Saud University Riyadh Kingdom of Saudi Arabia
                [ 6 ] Cardiac Sciences Department, Faculty of Medicine King Saud University Riyadh Kingdom of Saudi Arabia
                [ 7 ] Centre Hospitalier Provincial (CHP) de Taounate Taounate Maroc
                Author notes
                [*] [* ] Correspondence

                Abdelhabib Semlali, Groupe de Recherche en Écologie Buccale, Faculté de Médecine Dentaire, Université Laval, Québec, Québec, G1X OA6, Canada.

                Email: Abdelhabib.semlali@ 123456greb.ulaval.ca

                Author information
                https://orcid.org/0000-0002-5797-8304
                Article
                MGG3852
                10.1002/mgg3.852
                7650605
                31328431
                f6965610-e540-4457-a08b-c524ab6e79d1
                © 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 26 February 2019
                : 25 June 2019
                : 27 June 2019
                Page count
                Figures: 1, Tables: 7, Pages: 15, Words: 12105
                Funding
                Funded by: King Saud University , open-funder-registry 10.13039/501100002383;
                Award ID: RG-1440-044
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                September 2019
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.3 mode:remove_FC converted:09.11.2020

                cardiovascular disease,innate immune system,single‐nucleotide polymorphism,toll‐like receptor 4

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