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


Dunstan, SJ; Hue, NT; Han, B; Li, Z; Tram, TT; Sim, KS; Parry, CM; Chinh, NT; Vinh, H; Lan, NP; Thieu, NT; Vinh, PV; Koirala, S; Dongol, S; Arjyal, A; Karkey, A; Shilpakar, O; Dolecek, C; Foo, JN; Phuong, leT; Lanh, MN; Do, T; Aung, T; Hon, doN; Teo, YY; Hibberd, ML; Anders, KL; Okada, Y; Raychaudhuri, S; Simmons, CP; Baker, S; de Bakker, PI; Basnyat, B; Hien, TT; Farrar, JJ; Khor, CC; (2014) Variation at HLA-DRB1 is associated with resistance to enteric fever. Nature genetics, 46 (12). pp. 1333-6. ISSN 1061-4036 DOI: https://doi.org/10.1038/ng.3143

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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.<br/>

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
PubMed ID: 25383971
Web of Science ID: 345547300015
URI: http://researchonline.lshtm.ac.uk/id/eprint/2025533

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