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- Title
Variation at HLA-DRB1 is associated with resistance to enteric fever.
- Authors
Dunstan, Sarah J; Phuong, Le Thi; Lanh, Mai Ngoc; Do, Tan; Hon, Do Nu; Aung, Tin; Teo, Yik Ying; Hibberd, Martin L; Okada, Yukinori; Raychaudhuri, Soumya; Simmons, Cameron P; Baker, Stephen; de Bakker, Paul I W; Hue, Nguyen Thi; Khor, Chiea Chuen; Han, Buhm; Li, Zheng; Sim, Kar Seng; Foo, Jia Nee; Tram, Trinh Thi Bich
- 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 C1. 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.
- Subjects
TYPHOID fever; SALMONELLA enterica serovar Typhi; PUBLIC health -- Risk factors; INDUSTRIALIZATION; WATER purification
- Publication
Nature Genetics, 2014, Vol 46, Issue 12, p1333
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng.3143