european sarcoidosis gene discovered

Post here with questions about other autoimmune diseases or conditions.

Moderators: Mike Bartolatz, kwork

Post Reply
Mike Bartolatz
Posts: 6595
Joined: Fri Feb 06, 2004 9:58 pm

european sarcoidosis gene discovered

Post by Mike Bartolatz » Tue Jul 31, 2012 4:34 pm

A Novel Sarcoidosis Risk Locus for Europeans on Chromosome 11q13.1

Annegret Fischer1,
Benjamin Schmid2,
David Ellinghaus3,
Michael Nothnagel4,
Karoline I Gaede5,
Manfred Schürmann6,
Simone Lipinski7,
Philip Rosenstiel8,
Gernot Zissel9,
Kerstin Höhne10,
Martin Petrek11,
Vitezslav Kolek12,
Stefan Pabst13,
Christian Grohé14,
Johan Grunewald15,
Marcus Ronninger16,
Anders Eklund17,
Leonid Padyukov18,
Christian Gieger19,
H.-Erich Wichmann20,
Almut Nebel21,
Andre Franke22,
Joachim Müller-Quernheim23,
Sylvia Hofmann24 and
Stefan Schreiber25⇓

+ Author Affiliations

1Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany


2Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany


3Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany


4Institute of Medical Informatics and Statistics, Christian-Albrechts University, Kiel, Germany


5Department of Pneumology, Research Center Borstel, Borstel, Germany


6Institute of Human Genetics, University of Lübeck, Lübeck, Germany


7Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany


8Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany


9Department of Pneumology, University of Freiburg, Freiburg, Germany


10Department of Pneumology, University of Freiburg, Freiburg, Germany


11Laboratory of Immunogenetics and Immunoproteomics, Palacky University Olomouc, Olomouc, Czech Republic


12Department of Respiratory Medicine, Palacky University Olomouc, Olomouc, Czech Republic


13Department of Pneumology, University of Bonn, Bonn, Germany


14Department of Respiratory Medicine, Evangelische Lungenklinik Berlin-Buch, Berlin, Germany


15Department of Medicine, Karolinska Institutet, Stockholm, Sweden


16Department of Medicine, Karolinska Institutet, Stockholm, Sweden


17Department of Medicine, Karolinska Institutet, Stockholm, Sweden


18Department of Medicine, Karolinska Institutet, Stockholm, Sweden


19Institute of Genetic Epidemiology, German Research Center for Environmental Health, Neuherberg, Germany


20Institute of Medical Informatics, Ludwig-Maximilians University, Munich, Germany


21Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany


22Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany


23Department of Pneumology, University of Freiburg, Freiburg, Germany


24Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany


25Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany

Correspondence: Stefan Schreiber, Email: s.schreiber@mucosa.de


Abstract

Rationale: Sarcoidosis is a complex inflammatory disease with a heterogeneous clinical picture. Amongst others, an acute and chronic clinical course can be distinguished, for which specific genetic risk factors are known. Objectives: In order to identify additional risk loci for sarcoidosis and its acute and chronic subforms, we analyzed imputed data from a genome-wide association scan (GWAS) for these phenotypes. Methods: After quality control, the GWAS comprised nearly 1.3 million imputed single nucleotide polymorphisms based on an Affymetrix 6.0 Gene Chip dataset of 564 German sarcoidosis cases, including 176 acute and 354 chronic cases and 1575 controls. Main Results: We identified chromosome 11q13.1 (rs479777) as a novel locus influencing susceptibility to sarcoidosis with genome-wide significance. The marker was significantly associated in three distinct German case-control populations and in an additional German family sample with ORs ranging from 0.67 to 0.77. This finding was further replicated in two independent European case-control populations from the Czech Republic (OR = 0.75) and from Sweden (OR = 0.79). In a meta-analysis of the included European case-control samples the marker yielded a p value of 2.68x10-18. The locus was previously reported to be associated with Crohn´s disease, alopecia areata, leprosy and psoriasis. For sarcoidosis, fine-mapping and expression analysis suggest KCNK4, PRDX5, PCLB3 and, most promising, CCDC88B, as candidates for the underlying risk gene in the associated region. Conclusion: This study provides striking evidence for association of chromosome 11q13.1 with sarcoidosis in Europeans, and thus identified a further genetic risk locus shared by sarcoidosis, Crohn´s disease and psoriasis.
Received April 18, 2012.
Revision received July 5, 2012.
Accepted July 5, 2012.
Mike Bartolatz
Moderator

Post Reply