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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-03

AUTHORS

Gardar Sveinbjornsson, Daniel F Gudbjartsson, Bjarni V Halldorsson, Karl G Kristinsson, Magnus Gottfredsson, Jeffrey C Barrett, Larus J Gudmundsson, Kai Blondal, Arnaldur Gylfason, Sigurjon Axel Gudjonsson, Hafdis T Helgadottir, Adalbjorg Jonasdottir, Aslaug Jonasdottir, Ari Karason, Ljiljana Bulat Kardum, Jelena Knežević, Helgi Kristjansson, Mar Kristjansson, Arthur Love, Yang Luo, Olafur T Magnusson, Patrick Sulem, Augustine Kong, Gisli Masson, Unnur Thorsteinsdottir, Zlatko Dembic, Sergey Nejentsev, Thorsteinn Blondal, Ingileif Jonsdottir, Kari Stefansson

ABSTRACT

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. More... »

PAGES

318-322

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.3498

    DOI

    http://dx.doi.org/10.1038/ng.3498

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1001519781

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/26829749


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