Variation at HLA-DRB1 is associated with resistance to enteric fever

Enteric fever affects more than 25 million people annually and results from systemic infection with Salmonella enterica serovar Typhi or Paratyphi pathovars A, B or C(1). We conducted a genome-wide association study of 432 individuals with blood culture-confirmed enteric fever and 2,011 controls fro...

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1. Verfasser: Simmons, Cameron
Format: Journal Article
Sprache:Englisch
Veröffentlicht: 2018
Online-Zugang:https://demo7.dspace.org/handle/123456789/184
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author Simmons, Cameron
author_browse Simmons, Cameron
author_facet Simmons, Cameron
author_sort Simmons, Cameron
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description Enteric fever affects more than 25 million people annually and results from systemic infection with Salmonella enterica serovar Typhi or Paratyphi pathovars A, B or C(1). We conducted a genome-wide association study of 432 individuals with blood culture-confirmed enteric fever and 2,011 controls from Vietnam. We observed strong association at rs7765379 (odds ratio (OR) for the minor allele = 0.18, P = 4.5 × 10(-10)), a marker mapping to the HLA class II region, in proximity to HLA-DQB1 and HLA-DRB1. We replicated this association in 595 enteric fever cases and 386 controls from Nepal and also in a second independent collection of 151 cases and 668 controls from Vietnam. Imputation-based fine-mapping across the extended MHC region showed that the classical HLA-DRB1*04:05 allele (OR = 0.14, P = 2.60 × 10(-11)) could entirely explain the association at rs7765379, thus implicating HLA-DRB1 as a major contributor to resistance against enteric fever, presumably through antigen presentation.
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spelling oai:localhost:123456789-1842021-04-07T16:30:08Z Variation at HLA-DRB1 is associated with resistance to enteric fever Simmons, Cameron Enteric fever affects more than 25 million people annually and results from systemic infection with Salmonella enterica serovar Typhi or Paratyphi pathovars A, B or C(1). We conducted a genome-wide association study of 432 individuals with blood culture-confirmed enteric fever and 2,011 controls from Vietnam. We observed strong association at rs7765379 (odds ratio (OR) for the minor allele = 0.18, P = 4.5 × 10(-10)), a marker mapping to the HLA class II region, in proximity to HLA-DQB1 and HLA-DRB1. We replicated this association in 595 enteric fever cases and 386 controls from Nepal and also in a second independent collection of 151 cases and 668 controls from Vietnam. Imputation-based fine-mapping across the extended MHC region showed that the classical HLA-DRB1*04:05 allele (OR = 0.14, P = 2.60 × 10(-11)) could entirely explain the association at rs7765379, thus implicating HLA-DRB1 as a major contributor to resistance against enteric fever, presumably through antigen presentation. 2018-09-14T11:15:04Z 2017-07-12T03:29:04Z 2018-09-14T11:15:04Z 2014-10-15 2014-10-15 2014-10-15 2014-10-15 2014-10-15 2014-10-15 2014-10-15 2014-10-15 2014-12-01 Journal Article https://demo7.dspace.org/handle/123456789/184 English
spellingShingle Simmons, Cameron
Variation at HLA-DRB1 is associated with resistance to enteric fever
title Variation at HLA-DRB1 is associated with resistance to enteric fever
title_full Variation at HLA-DRB1 is associated with resistance to enteric fever
title_fullStr Variation at HLA-DRB1 is associated with resistance to enteric fever
title_full_unstemmed Variation at HLA-DRB1 is associated with resistance to enteric fever
title_short Variation at HLA-DRB1 is associated with resistance to enteric fever
title_sort variation at hla drb1 is associated with resistance to enteric fever
url https://demo7.dspace.org/handle/123456789/184
work_keys_str_mv AT simmonscameron variationathladrb1isassociatedwithresistancetoentericfever