| Literature DB >> 25383971 |
Sarah J Dunstan1, Nguyen Thi Hue2, Buhm Han3, Zheng Li4, Trinh Thi Bich Tram5, Kar Seng Sim4, Christopher M Parry6, Nguyen Tran Chinh7, Ha Vinh7, Nguyen Phu Huong Lan7, Nga Tran Vu Thieu5, Phat Voong Vinh5, Samir Koirala8, Sabina Dongol8, Amit Arjyal8, Abhilasha Karkey8, Olita Shilpakar8, Christiane Dolecek9, Jia Nee Foo4, Le Thi Phuong10, Mai Ngoc Lanh10, Tan Do11, Tin Aung12, Do Nu Hon11, Yik Ying Teo13, Martin L Hibberd14, Katherine L Anders9, Yukinori Okada15, Soumya Raychaudhuri16, Cameron P Simmons17, Stephen Baker18, Paul I W de Bakker19, Buddha Basnyat8, Tran Tinh Hien5, Jeremy J Farrar9, Chiea Chuen Khor20.
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.Entities:
Mesh：
Substances：
Year: 2014 PMID： 25383971 PMCID： PMC5099079 DOI： 10.1038/ng.3143
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330