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

被引：78

作者：

Dunstan, Sarah J. ^{[1
,2
,3
]}

Nguyen Thi Hue ^{[1
,4
]}

Buhm Han ^{[5
,6
,7
,8
]}

Li, Zheng ^{[9
]}

Trinh Thi Bich Tram ^{[1
]}

Sim, Kar Seng ^{[9
]}

Parry, Christopher M. ^{[1
,10
]}

Nguyen Tran Chinh ^{[11
]}

Ha Vinh ^{[11
]}

Nguyen Phu Huong Lan ^{[11
]}

Nga Tran Vu Thieu ^{[1
]}

Phat Voong Vinh ^{[1
]}

Koirala, Samir ^{[12
]}

Dongol, Sabina ^{[12
]}

Arjyal, Amit ^{[12
]}

Karkey, Abhilasha ^{[12
]}

Shilpakar, Olita ^{[12
]}

Dolecek, Christiane ^{[1
,2
]}

Foo, Jia Nee ^{[9
]}

Le Thi Phuong ^{[13
]}

Mai Ngoc Lanh ^{[13
]}

Tan Do ^{[14
]}

Aung, Tin ^{[15
]}

Do Nu Hon ^{[14
]}

Teo, Yik Ying ^{[16
,17
]}

Hibberd, Martin L. ^{[9
,18
]}

Anders, Katherine L. ^{[1
,2
]}

Okada, Yukinori ^{[19
,20
]}

Raychaudhuri, Soumya ^{[6
,7
,8
,21
,22
]}

Simmons, Cameron P. ^{[1
,2
,23
]}

Baker, Stephen ^{[1
,2
,18
]}

de Bakker, Paul I. W. ^{[24
,25
]}

Basnyat, Buddha ^{[12
]}

Tran Tinh Hien ^{[1
]}

Farrar, Jeremy J. ^{[1
,2
]}

Khor, Chiea Chuen ^{[9
,15
,17
,26
,27
]}

机构：

[1] Hosp Trop Dis, Oxford Univ Clin Res Unit, Ho Chi Minh City, Vietnam

[2] Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford, England

[3] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Nossal Inst Global Hlth, Melbourne, Vic, Australia

[4] Vietnam Natl Univ, Univ Sci, Fac Biol, Ho Chi Minh City, Vietnam

[5] Univ Ulsan, Coll Med, Asan Med Ctr, Asan Inst Life Sci, Seoul, South Korea

[6] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Genet, Boston, MA 02115 USA

[7] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA

[8] Partners Ctr Personalized Genet Med, Boston, MA USA

[9] Genome Inst Singapore, Singapore, Singapore

[10] Univ Liverpool, Liverpool Sch Trop Med, Liverpool L3 5QA, Merseyside, England

[11] Hosp Trop Dis, Ho Chi Minh City, Vietnam

[12] Patan Hosp, Patan Acad Hlth Sci, Oxford Univ Clin Res Unit Nepal, Patan, Nepal

[13] Dong Thap Prov Hosp, Cao Lanh, Vietnam

[14] Vietnam Natl Inst Ophthalmol, Hanoi, Vietnam

[15] Singapore Eye Res Inst, Singapore, Singapore

[16] Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore 117548, Singapore

[17] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore

[18] Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England

[19] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Human Genet & Dis Divers, Tokyo, Japan

[20] RIKEN Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan

[21] Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA

[22] Univ Manchester, Fac Med & Human Sci, Manchester, Lancs, England

[23] Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic, Australia

[24] Univ Med Ctr Utrecht, Ctr Mol Med, Dept Med Genet, Utrecht, Netherlands

[25] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, Utrecht, Netherlands

[26] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Paediat, Singapore 117595, Singapore

[27] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore 117595, Singapore

来源：

NATURE GENETICS | 2014年 / 46卷 / 12期

基金：

英国惠康基金;

关键词：

GENOME-WIDE ASSOCIATION; TYPHOID-FEVER; COMMON VARIANTS; SUSCEPTIBILITY LOCI; CLASS-II; HLA; SALMONELLA; DISEASE; REGION; DETERMINANTS;

D O I：

10.1038/ng.3143

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 x 10(-10)), a marker mapping to the H LA 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 x 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.

引用

页码：1333 / 1336

页数：4

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