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


ABSTRACT: 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.

SUBMITTER: Dunstan SJ 

PROVIDER: S-EPMC5099079 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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

Dunstan Sarah J SJ   Hue Nguyen Thi NT   Han Buhm B   Li Zheng Z   Tram Trinh Thi Bich TT   Sim Kar Seng KS   Parry Christopher M CM   Chinh Nguyen Tran NT   Vinh Ha H   Lan Nguyen Phu Huong NP   Thieu Nga Tran Vu NT   Vinh Phat Voong PV   Koirala Samir S   Dongol Sabina S   Arjyal Amit A   Karkey Abhilasha A   Shilpakar Olita O   Dolecek Christiane C   Foo Jia Nee JN   Phuong Le Thi le T   Lanh Mai Ngoc MN   Do Tan T   Aung Tin T   Hon Do Nu DN   Teo Yik Ying YY   Hibberd Martin L ML   Anders Katherine L KL   Okada Yukinori Y   Raychaudhuri Soumya S   Simmons Cameron P CP   Baker Stephen S   de Bakker Paul I W PI   Basnyat Buddha B   Hien Tran Tinh TT   Farrar Jeremy J JJ   Khor Chiea Chuen CC  

Nature genetics 20141110 12


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-D  ...[more]

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