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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
A TNF region haplotype offers protection from typhoid fever in Vietnamese patients
Human Genetics, Volume 122, No. 1, Year 2007
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Description
The genomic region surrounding the TNF locus on human chromosome 6 has previously been associated with typhoid fever in Vietnam (Dunstan et al. in J Infect Dis 183:261-268, 2001). We used a haplotypic approach to understand this association further. Eighty single nucleotide polymorphisms (SNPs) spanning a 150 kb region were genotyped in 95 Vietnamese individuals (typhoid case/mother/father trios). A subset of data from 33 SNPs with a minor allele frequency of >4.3% was used to construct haplotypes. Fifteen SNPs, which tagged the 42 constructed haplotypes were selected. The haplotype tagging SNPs (T1-T15) were genotyped in 380 confirmed typhoid cases and 380 Vietnamese ethnically matched controls. Allelic frequencies of seven SNPs (T1, T2, T3, T5, T6, T7, T8) were significantly different between typhoid cases and controls. Logistic regression results support the hypothesis that there is just one signal associated with disease at this locus. Haplotype-based analysis of the tag SNPs provided positive evidence of association with typhoid (posterior probability 0.821). The analysis highlighted a low-risk cluster of haplotypes that each carry the minor allele of T1 or T7, but not both, and otherwise carry the combination of alleles *12122*1111 at T1-T11, further supporting the one associated signal hypothesis. Finally, individuals that carry the typhoid fever protective haplotype *12122*1111 also produce a relatively low TNF-α response to LPS. © Springer-Verlag 2007.
Authors & Co-Authors
Dunstan, Sarah J.
United Kingdom, London
University College London Hospitals Nhs Foundation Trust
United Kingdom, Oxford
University of Oxford
Rockett, Kirk A.
United Kingdom, Oxford
University of Oxford
Forton, Julian T.
United Kingdom, Oxford
University of Oxford
Morris, Andrew Paul
United Kingdom, Oxford
University of Oxford
Diakité, Mahamadou L.
United Kingdom, Oxford
University of Oxford
Parry, Christopher Mark
United Kingdom, Liverpool
University of Liverpool
Vinh, Ha
United Kingdom, London
University College London Hospitals Nhs Foundation Trust
Hieu, Nguyen Trong
Viet Nam, Ho Chi Minh City
Hung Vuong Hospital
Dougan, Gordon J.
United Kingdom, Hinxton
Wellcome Sanger Institute
Hien, Tran Tinh
United Kingdom, London
University College London Hospitals Nhs Foundation Trust
Farrar, Jeremy James
United Kingdom, Oxford
University of Oxford
Statistics
Citations: 20
Authors: 11
Affiliations: 5
Identifiers
Doi:
10.1007/s00439-007-0372-9
ISSN:
03406717
Research Areas
Genetics And Genomics
Infectious Diseases