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  Immunochip SNP array identifies novel genetic variants conferring susceptibility to candidaemia

Kumar, V., Cheng, S.-C., Johnson, M. D., Smeekens, S., Wojtowicz, A., Giamarellos-Bourboulis, E., et al. (2014). Immunochip SNP array identifies novel genetic variants conferring susceptibility to candidaemia. Nature Communications, 5: 5:4675. doi:10.1038/ncomms5675.

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© 2014 Macmillan Publishers Limited
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 Urheber:
Kumar, Vinod, Autor
Cheng, Shih-Chin, Autor
Johnson, Melissa D., Autor
Smeekens, Sanne, Autor
Wojtowicz, Agnieszka, Autor
Giamarellos-Bourboulis, Evangelos, Autor
Karjalainen, Juha, Autor
Franke, Lude, Autor
Withoff, Sebo, Autor
Plantinga, Theo S., Autor
van de Veerdonk, Frank, Autor
van der Meer, Jos, Autor
Joosten, Leo A. B., Autor
Sokol, Harry, Autor
Bauer, Hermann1, Autor           
Herrmann, Bernhard G.1, Autor           
Bochud, Pierre-Yves, Autor
Marchetti, Oscar, Autor
Perfect, John R., Autor
Xavier, Ramnik, Autor
Kullberg, Bart Jan, AutorWijmenga, Cisca, AutorNetea, Mihai, Autor mehr..
Affiliations:
1Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433548              

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 Zusammenfassung: Candidaemia is the fourth most common cause of bloodstream infection, with a high mortality rate of up to 40%. Identification of host genetic factors that confer susceptibility to candidaemia may aid in designing adjunctive immunotherapeutic strategies. Here we hypothesize that variation in immune genes may predispose to candidaemia. We analyse 118,989 single-nucleotide polymorphisms (SNPs) across 186 loci known to be associated with immune-mediated diseases in the largest candidaemia cohort to date of 217 patients of European ancestry and a group of 11,920 controls. We validate the significant associations by comparison with a disease-matched control group. We observe significant association between candidaemia and SNPs in the ​CD58 (P=1.97 × 10−11; odds ratio (OR)=4.68), ​LCE4A-​C1orf68 (P=1.98 × 10−10; OR=4.25) and ​TAGAP (P=1.84 × 10−8; OR=2.96) loci. Individuals carrying two or more risk alleles have an increased risk for candidaemia of 19.4-fold compared with individuals carrying no risk allele. We identify three novel genetic risk factors for candidaemia, which we subsequently validate for their role in antifungal host defence.

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 Datum: 2014-09-08
 Publikationsstatus: Online veröffentlicht
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 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: DOI: 10.1038/ncomms5675
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Titel: Nature Communications
  Kurztitel : Nat. Commun.
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: London : Nature Publishing Group
Seiten: - Band / Heft: 5 Artikelnummer: 5:4675 Start- / Endseite: - Identifikator: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723