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

http://repository.vnu.edu.vn/handle/VNU_123/29569

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 â '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 â '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

Title: Variation at HLA-DRB1 is associated with resistance to enteric fever
Authors: Dunstan, Sarah J
Sarah J, Nguyen Thi
Han, Buhm
Li, Zheng
Keywords: HLA DPB1 antigen
HLA DQA1 antigen
biological marker
genetic marker
Issue Date: 2014
Publisher: Nature Genetics
Citation: Scopus
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 â '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 â '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
Description: Nature Genetics Volume 46, Issue 12, 11 December 2014, Pages 1333-1336
Nature Genetics
URI: http://repository.vnu.edu.vn/handle/VNU_123/29569
ISSN: 10614036
Appears in Collections:Bài báo của ĐHQGHN trong Scopus

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