title: Granuloma genes in sarcoidosis: what is new?
abstract: OBJECTIVE
  Nonnecrotizing granulomas in the affected organ are the hallmark of sarcoidosis. This review summarizes most recent genetic findings in sarcoidosis with a focus on genes that might influence granuloma formation or resolution. Specific results in multiple ethnic groups and certain clinical subphenotypes, such as extra-pulmonary organ involvement, are discussed.
  
  
  RESULTS
  Associations of genetic variants in antigen-presenting molecules (HLA-DRB1) were shown to confer risk to sarcoidosis and certain disease phenotypes in populations of different ethnic origins. Specific DRB1 alleles, such as *0301 and *0302, appear to confer protection against chronic disease, but in an ethnic-specific manner illustrating the extensive genetic heterogeneity and complexity at this locus. Mechanistic studies of putative sarcoid antigens lend further credence to a role of HLA-DRB1 in disease pathogenesis. With relevance to granuloma formation, genes involved in apoptotic processes and immune cell activation were further confirmed (ANXA11 and BTNL2) in multiple ethnicities; others were newly identified (XAF1). Linking mechanism to clinical application, a TNF variant was shown to correlate with anti-TNF response in sarcoidosis patients.
  
  
  CONCLUSIONS
  The investigation of known and novel risk variants for sarcoidosis and specific clinical phenotypes in various ethnicities highlights the genetic complexity of the disease. Detailed subanalysis of disease phenotypes revealed the potential for prediction of extra-pulmonary organ involvement and therapy response based on the patient's genotype.
authors.affiliation: aInstitute of Clinical Molecular Biology, Kiel University, Kiel, Germany bDepartment of Public Health Sciences, Henry Ford Hospital, Detroit, Michigan, USA.
authors.forename: Annegret
authors.initials: A
authors.lastname: Fischer
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Rybicki
mesh_terms: D000483:Alleles; D006099:Granuloma / Q000235:genetics* / Q000473:pathology; D059811:HLA-DRB1 Chains / Q000235:genetics; D006801:Humans; D008213:Lymphocyte Activation; D012507:Sarcoidosis / Q000235:genetics* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D059811:HLA-DRB1 Chains; D014409:Tumor Necrosis Factor-alpha