Toll-like receptor 4 (TLR4) and typhoid fever in Vietnam
Understanding the host genetic susceptibility to typhoid fever may provide a better understanding of pathogenesis and help in the development of new therapeutics and vaccines. Here we determine the genetic variation within the human TLR4 gene encoding the principal receptor for bacterial endotoxin r...
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Published in | PloS one Vol. 4; no. 3; p. e4800 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
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Public Library of Science
11.03.2009
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Abstract | Understanding the host genetic susceptibility to typhoid fever may provide a better understanding of pathogenesis and help in the development of new therapeutics and vaccines. Here we determine the genetic variation within the human TLR4 gene encoding the principal receptor for bacterial endotoxin recognition in typhoid fever patients. It is possible that genetic variants of TLR4 could detrimentally affect the innate immune response against S. typhi infection. Mutation detection and genotyping of TLR4 was performed on DNA from 414 Vietnamese typhoid fever patients and 372 population controls. dHPLC detected a total of 10 polymorphisms within the upstream and exonic regions of TLR4, of which 7 are novel. Two SNPs, T4025A and C4215G, were more frequent in typhoid cases than in controls however due to their low allele frequencies they showed borderline significance (T4025A: OR 1.9, 95%CI 0.9-4.3, P 0.07 and C4215G: OR 6.7, 95%CI 0.8-307, P 0.04). Six missense mutations were identified, with 5/6 positioned in the ectoplasmic domain. Four missense mutations and one promoter SNP (A-271G) were only present in typhoid cases, albeit at low allele frequencies. Here we determined the extent of genetic variation within TLR4 in a Vietnamese population and suggest that TLR4 may be involved in defense against typhoid fever in this population. |
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AbstractList | Understanding the host genetic susceptibility to typhoid fever may provide a better understanding of pathogenesis and help in the development of new therapeutics and vaccines. Here we determine the genetic variation within the human TLR4 gene encoding the principal receptor for bacterial endotoxin recognition in typhoid fever patients. It is possible that genetic variants of TLR4 could detrimentally affect the innate immune response against S. typhi infection. Mutation detection and genotyping of TLR4 was performed on DNA from 414 Vietnamese typhoid fever patients and 372 population controls. dHPLC detected a total of 10 polymorphisms within the upstream and exonic regions of TLR4, of which 7 are novel. Two SNPs, T4025A and C4215G, were more frequent in typhoid cases than in controls however due to their low allele frequencies they showed borderline significance (T4025A: OR 1.9, 95%CI 0.9-4.3, P 0.07 and C4215G: OR 6.7, 95%CI 0.8-307, P 0.04). Six missense mutations were identified, with 5/6 positioned in the ectoplasmic domain. Four missense mutations and one promoter SNP (A-271G) were only present in typhoid cases, albeit at low allele frequencies. Here we determined the extent of genetic variation within TLR4 in a Vietnamese population and suggest that TLR4 may be involved in defense against typhoid fever in this population. Understanding the host genetic susceptibility to typhoid fever may provide a better understanding of pathogenesis and help in the development of new therapeutics and vaccines. Here we determine the genetic variation within the human TLR4 gene encoding the principal receptor for bacterial endotoxin recognition in typhoid fever patients. It is possible that genetic variants of TLR4 could detrimentally affect the innate immune response against S. typhi infection. Mutation detection and genotyping of TLR4 was performed on DNA from 414 Vietnamese typhoid fever patients and 372 population controls. dHPLC detected a total of 10 polymorphisms within the upstream and exonic regions of TLR4 , of which 7 are novel. Two SNPs, T4025A and C4215G, were more frequent in typhoid cases than in controls however due to their low allele frequencies they showed borderline significance (T4025A: OR 1.9, 95%CI 0.9–4.3, P 0.07 and C4215G: OR 6.7, 95%CI 0.8–307, P 0.04). Six missense mutations were identified, with 5/6 positioned in the ectoplasmic domain. Four missense mutations and one promoter SNP (A-271G) were only present in typhoid cases, albeit at low allele frequencies. Here we determined the extent of genetic variation within TLR4 in a Vietnamese population and suggest that TLR4 may be involved in defense against typhoid fever in this population. |
Audience | Academic |
Author | Le, Thi Phuong Nguyen, Tran Chinh Tran, Tinh Hien Farrar, Jeremy J Dunstan, Sarah J Mai, Ngoc Lanh Ha, Vinh Nguyen, T Hieu Nguyen, Thi Hue |
AuthorAffiliation | 4 Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, Oxford, United Kingdom 2 Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam University of Toronto, Canada 1 Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam 3 Dong Thap Provincial Hospital, Dong Thap, Vietnam 5 Hung Vuong Hospital, Ho Chi Minh City, Vietnam |
AuthorAffiliation_xml | – name: 5 Hung Vuong Hospital, Ho Chi Minh City, Vietnam – name: 1 Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam – name: 2 Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam – name: 4 Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, Oxford, United Kingdom – name: University of Toronto, Canada – name: 3 Dong Thap Provincial Hospital, Dong Thap, Vietnam |
Author_xml | – sequence: 1 givenname: Thi Hue surname: Nguyen fullname: Nguyen, Thi Hue organization: Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam – sequence: 2 givenname: Ngoc Lanh surname: Mai fullname: Mai, Ngoc Lanh – sequence: 3 givenname: Thi Phuong surname: Le fullname: Le, Thi Phuong – sequence: 4 givenname: Vinh surname: Ha fullname: Ha, Vinh – sequence: 5 givenname: Tran Chinh surname: Nguyen fullname: Nguyen, Tran Chinh – sequence: 6 givenname: Tinh Hien surname: Tran fullname: Tran, Tinh Hien – sequence: 7 givenname: T Hieu surname: Nguyen fullname: Nguyen, T Hieu – sequence: 8 givenname: Jeremy J surname: Farrar fullname: Farrar, Jeremy J – sequence: 9 givenname: Sarah J surname: Dunstan fullname: Dunstan, Sarah J |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/19277200$$D View this record in MEDLINE/PubMed |
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Copyright | COPYRIGHT 2009 Public Library of Science 2009 Hue et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. Hue et al. 2009 |
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SubjectTerms | Alleles Bacteria Burns Case-Control Studies Clinical medicine Cytokines Deoxyribonucleic acid Disease susceptibility DNA DNA Mutational Analysis Drug development Endotoxins Ethnic Groups - genetics Exons - genetics Female Fever Gene expression Gene Frequency Genes Genetic aspects Genetic diversity Genetic Predisposition to Disease Genetic variance Genetics and Genomics/Genetics of Disease Genotype Genotyping Health aspects Hospitals Humans Immune response Immune system Immunology/Immunity to Infections Immunology/Innate Immunity Infections Infectious diseases Infectious Diseases/Bacterial Infections Innate immunity Legionnaires disease Male Medicine Meningitis Missense mutation Mutation Mutation, Missense Pathogenesis Patients Polymorphism, Single Nucleotide Promoter Regions, Genetic - genetics Protein Structure, Tertiary Proteins Salmonella Salmonella Typhimurium Sepsis Single-nucleotide polymorphism Studies TLR4 protein Toll-Like Receptor 4 - genetics Toll-Like Receptor 4 - physiology Toll-like receptors Transcription factors Tropical diseases Typhoid Typhoid fever Typhoid Fever - epidemiology Typhoid Fever - genetics Vaccines Vietnam - epidemiology Waterborne diseases |
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Title | Toll-like receptor 4 (TLR4) and typhoid fever in Vietnam |
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