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 inPloS one Vol. 4; no. 3; p. e4800
Main Authors Nguyen, Thi Hue, Mai, Ngoc Lanh, Le, Thi Phuong, Ha, Vinh, Nguyen, Tran Chinh, Tran, Tinh Hien, Nguyen, T Hieu, Farrar, Jeremy J, Dunstan, Sarah J
Format Journal Article
LanguageEnglish
Published United States 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.
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
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– name: 1 Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/19277200$$D View this record in MEDLINE/PubMed
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Snippet Understanding the host genetic susceptibility to typhoid fever may provide a better understanding of pathogenesis and help in the development of new...
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StartPage e4800
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
URI https://www.ncbi.nlm.nih.gov/pubmed/19277200
https://www.proquest.com/docview/1290025555
https://search.proquest.com/docview/67016518
https://pubmed.ncbi.nlm.nih.gov/PMC2652111
https://doaj.org/article/d87c56ad9f514a34a972ece7815d7b7a
http://dx.doi.org/10.1371/journal.pone.0004800
Volume 4
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