Variation at HLA-DRB1 is associated with resistance to enteric fever.
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 fro...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Nature Publishing Group
2014
|
| _version_ | 1826271749771100160 |
|---|---|
| author | Dunstan, S Hue, N Han, B Li, Z Tram, T Sim, K Parry, C Chinh, N Vinh, H Lan, N Thieu, N Vinh, P Koirala, S Dongol, S Arjyal, A Karkey, A Shilpakar, O Dolecek, C Foo, J Phuong, LT Lanh, M Do, T Aung, T Hon, D Teo, Y |
| author_facet | Dunstan, S Hue, N Han, B Li, Z Tram, T Sim, K Parry, C Chinh, N Vinh, H Lan, N Thieu, N Vinh, P Koirala, S Dongol, S Arjyal, A Karkey, A Shilpakar, O Dolecek, C Foo, J Phuong, LT Lanh, M Do, T Aung, T Hon, D Teo, Y |
| author_sort | Dunstan, S |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T22:01:36Z |
| format | Journal article |
| id | oxford-uuid:4ec8fa35-a8ab-4af4-8bbc-f9b9757f21a0 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:01:36Z |
| publishDate | 2014 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:4ec8fa35-a8ab-4af4-8bbc-f9b9757f21a02022-03-26T16:03:16ZVariation at HLA-DRB1 is associated with resistance to enteric fever.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4ec8fa35-a8ab-4af4-8bbc-f9b9757f21a0EnglishSymplectic Elements at OxfordNature Publishing Group2014Dunstan, SHue, NHan, BLi, ZTram, TSim, KParry, CChinh, NVinh, HLan, NThieu, NVinh, PKoirala, SDongol, SArjyal, AKarkey, AShilpakar, ODolecek, CFoo, JPhuong, LTLanh, MDo, TAung, THon, DTeo, YEnteric 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. |
| spellingShingle | Dunstan, S Hue, N Han, B Li, Z Tram, T Sim, K Parry, C Chinh, N Vinh, H Lan, N Thieu, N Vinh, P Koirala, S Dongol, S Arjyal, A Karkey, A Shilpakar, O Dolecek, C Foo, J Phuong, LT Lanh, M Do, T Aung, T Hon, D Teo, Y Variation at HLA-DRB1 is associated with resistance to enteric fever. |
| title | Variation at HLA-DRB1 is associated with resistance to enteric fever. |
| title_full | Variation at HLA-DRB1 is associated with resistance to enteric fever. |
| title_fullStr | Variation at HLA-DRB1 is associated with resistance to enteric fever. |
| title_full_unstemmed | Variation at HLA-DRB1 is associated with resistance to enteric fever. |
| title_short | Variation at HLA-DRB1 is associated with resistance to enteric fever. |
| title_sort | variation at hla drb1 is associated with resistance to enteric fever |
| work_keys_str_mv | AT dunstans variationathladrb1isassociatedwithresistancetoentericfever AT huen variationathladrb1isassociatedwithresistancetoentericfever AT hanb variationathladrb1isassociatedwithresistancetoentericfever AT liz variationathladrb1isassociatedwithresistancetoentericfever AT tramt variationathladrb1isassociatedwithresistancetoentericfever AT simk variationathladrb1isassociatedwithresistancetoentericfever AT parryc variationathladrb1isassociatedwithresistancetoentericfever AT chinhn variationathladrb1isassociatedwithresistancetoentericfever AT vinhh variationathladrb1isassociatedwithresistancetoentericfever AT lann variationathladrb1isassociatedwithresistancetoentericfever AT thieun variationathladrb1isassociatedwithresistancetoentericfever AT vinhp variationathladrb1isassociatedwithresistancetoentericfever AT koiralas variationathladrb1isassociatedwithresistancetoentericfever AT dongols variationathladrb1isassociatedwithresistancetoentericfever AT arjyala variationathladrb1isassociatedwithresistancetoentericfever AT karkeya variationathladrb1isassociatedwithresistancetoentericfever AT shilpakaro variationathladrb1isassociatedwithresistancetoentericfever AT dolecekc variationathladrb1isassociatedwithresistancetoentericfever AT fooj variationathladrb1isassociatedwithresistancetoentericfever AT phuonglt variationathladrb1isassociatedwithresistancetoentericfever AT lanhm variationathladrb1isassociatedwithresistancetoentericfever AT dot variationathladrb1isassociatedwithresistancetoentericfever AT aungt variationathladrb1isassociatedwithresistancetoentericfever AT hond variationathladrb1isassociatedwithresistancetoentericfever AT teoy variationathladrb1isassociatedwithresistancetoentericfever |