Genotype-Phenotype Relationship in Sarcoidosis

• Applicant: Professor Dr. Joachim Müller-Quernheim
• Subject Area: Pneumology, Thoracic Surgery
• Term: from 2008 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 44710924

Sarcoidosis is a systemic granulomatous disorder of unknown aetiology, preferentially affecting the lung. The disease has a wide spectrum of clinical courses, ranging from spontaneous remission to disabling organ damage or even death. There is accumulating evidence for a genetic susceptibility to sarcoidosis, including an association with genes in the major histocompatibility complex (MHC). In a genome-wide linkage study, we recognized seven chromosomal regions of aetiological relevance and recently identified BTNL2 as a new sarcoidosis disease gene on chromosome 6. In a genome-wide association study using 100K Affymetrix micro-arrays, we uncovered two additional susceptibility regions on chromosomes 7 and 10. In the present project, 2000 sarcoidosis patients will be extracted from a cohort of 5570 prevalent cases and genotyped for MHC genes, BTNL2, and an estimated 15 new positional candidate genes from our genome-wide 500K SNP chip studies and ongoing replication. Patients will be phenotyped at 31 study sites according to a standardized protocol and the relationship between their phenotype and genotype will be assessed. In particular, genotypes of patients with rare, unfavourable and chronic disease courses, including cardiac, neurological, cutaneous, and therapy-resistant manifestations, will be compared to those associated with spontaneous resolution. The patient cohort will be large enough to contain a sufficiently large number of rare phenotypes so as to ensure prognostic usefulness of the respective results. In practise, patients with adverse genotypes should be intensely monitored and would benefit most from new therapeutic approaches.

• DFG Programme: Clinical Trials