HLA class II sequence variants influence tuberculosis risk in populations of European ancestry

Autor: Ari Karason, Jeffrey C. Barrett, Daniel F. Gudbjartsson, Unnur Thorsteinsdottir, Adalbjorg Jonasdottir, Kai Blöndal, Olafur Th Magnusson, Aslaug Jonasdottir, Hafdis T. Helgadottir, Larus J. Gudmundsson, Helgi Kristjansson, Yang Luo, Kari Stefansson, Gardar Sveinbjornsson, Gisli Masson, Mar Kristjansson, Arnaldur Gylfason, Augustine Kong, Ljiljana Bulat Kardum, Sigurjon A. Gudjonsson, Ingileif Jonsdottir, Arthur Löve, Jelena Knežević, Magnus Gottfredsson, Bjarni V. Halldorsson, Thorsteinn Blondal, Zlatko Dembic, Sergey Nejentsev, Karl G. Kristinsson, Patrick Sulem
Přispěvatelé: [ 1 ] Amgen Inc, deCODE Genet, Reykjavik, Iceland [ 2 ] Univ Iceland, Sch Engn & Nat Sci, Reykjavik, Iceland [ 3 ] Reykjavik Univ, Sch Sci & Engn, Reykjavik, Iceland [ 4 ] Univ Iceland, Sch Hlth Sci, Fac Med, Reykjavik, Iceland [ 5 ] Natl Univ Hosp Iceland, Dept Clin Microbiol, Landspitali, Reykjavik, Iceland [ 6 ] Natl Univ Hosp Iceland, Dept Infect Dis, Landspitali, Reykjavik, Iceland [ 7 ] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton, England [ 8 ] Primary Hlth Care Capital Area, Div Communicable Dis Prevent & Control, Reykjavik, Iceland [ 9 ] Univ Rijeka, Dept Pulmonol, Clin Internal Med, Clin Hosp Ctr, Rijeka, Croatia [ 10 ] Univ Oslo, Fac Dent, Dept Oral Biol, Mol Genet Lab, Oslo, Norway [ 11 ] Rudjer Boskovic Inst, Div Mol Med, Zagreb, Croatia [ 12 ] Natl Univ Hosp Iceland, Landspitali, Dept Virol, Reykjavik, Iceland Organization-Enhanced Name(s) Landspitali National University Hospital [ 13 ] Univ Cambridge, Dept Med, Cambridge CB2 2QQ, England [ 14 ] Natl Univ Hosp Iceland, Landspitali, Dept Immunol, Reykjavik, Iceland Organization-Enhanced Name(s) Landspitali National University Hospital
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences
T-Lymphocytes
Iceland
Genome-wide association study
TMD12
0302 clinical medicine
Gene Frequency
Risk Factors
Genetics
variants
BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti
Berklar
3. Good health
Europe
BAC12
tuberculosis
030220 oncology & carcinogenesis
NAF12
BIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti
Tuberculosis
Human leukocyte antigen
Biology
Article
HLA-DQ alpha-Chains
White People
03 medical and health sciences
Antigen
medicine
Humans
Genetic Predisposition to Disease
HLA class II
Allele
Tuberculosis
Pulmonary
Allele frequency
Alleles
PAD12
Genome
Human
HLA-DR Antigens/genetics
BIOMEDICINE AND HEALTHCARE. Basic Medical Sciences
Genetic Variation
Mycobacterium tuberculosis
Odds ratio
Arfgengi
medicine.disease
Virology
Tuberculosis
Pulmonary/genetics
Minor allele frequency
030104 developmental biology
Genome-Wide Association Study
HLA-DRB1 Chains
Zdroj: Nature genetics
Volume 48
Issue 3
ISSN: 1061-4036
Popis: To access publisher's full text version of this article click on the hyperlink at the bottom of the page Mycobacterium tuberculosis infections cause 9 million new tuberculosis cases and 1.5 million deaths annually. To identify variants conferring risk of tuberculosis, we tested 28.3 million variants identified through whole-genome sequencing of 2,636 Icelanders for association with tuberculosis (8,162 cases and 277,643 controls), pulmonary tuberculosis (PTB) and M. tuberculosis infection. We found association of three variants in the region harboring genes encoding the class II human leukocyte antigens (HLAs): rs557011[T] (minor allele frequency (MAF) = 40.2%), associated with M. tuberculosis infection (odds ratio (OR) = 1.14, P = 3.1 × 10(-13)) and PTB (OR = 1.25, P = 5.8 × 10(-12)), and rs9271378[G] (MAF = 32.5%), associated with PTB (OR = 0.78, P = 2.5 × 10(-12))-both located between HLA-DQA1 and HLA-DRB1-and a missense variant encoding p.Ala210Thr in HLA-DQA1 (MAF = 19.1%, rs9272785), associated with M. tuberculosis infection (P = 9.3 × 10(-9), OR = 1.14). We replicated association of these variants with PTB in samples of European ancestry from Russia and Croatia (P < 5.9 × 10(-4)). These findings show that the HLA class II region contributes to genetic risk of tuberculosis, possibly through reduced presentation of protective M. tuberculosis antigens to T cells. US National Institute of Allergy and Infectious Diseases HHSN266200400064C UK Wellcome Trust 088838/Z/09/Z 095198/Z/10/Z info:eu-repo/grantAgreement/EC/FP7/201483 European Research Council Starting 260477 Royal Society UF0763346 RG090638 Wellcome Trust Senior Research fellowship National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre
Databáze: OpenAIRE
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