title: Genetics of Behçet's disease: lessons learned from genomewide association studies.
abstract: OBJECTIVE
  Behçet's disease is a complex disease, and genetic susceptibility plays a critical role. This review aimed to discuss the recent genomewide association study (GWAS) findings and their implications to the pathogenesis of Behçet's disease.
  
  
  RESULTS
  GWAS data confirmed the major role of HLA-B51 in Behçet's disease susceptibility, and the discovery of epistatic interactions between HLA-B51 and ERAP1 variants provided some hints about its possible pathogenic mechanisms. Investigation of human leukocyte antigen (HLA) Class I region showed weaker but independent associations around HLA-A and HLA-C regions. Genomewide studies also established associations with IL10, IL23R, CCR1, STAT4, KLRC4, GIMAP2/GIMAP4, and UBAC2 genes in Behçet's disease patients of different ethnicities. Deep resequencing of targeted genes identified additional associations with rare variants in TLR4, MEFV, and NOD2 genes.
  
  
  CONCLUSIONS
  GWAS data established a major step forward by providing insights into the underlying mechanisms in Behçet's disease with the discovery of new susceptibility genes. These variations may implicate defects in the sensing and processing of microbial and endogenous danger signals as well as in the regulation of innate and adaptive immune responses in Behçet's disease. Association findings with HLA Class I antigens as well as IL23R, ERAP1, IL10, and MEFV genes also suggest shared inflammatory pathways with spondyloarthropathies.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Gül
mesh_terms: D000626:Aminopeptidases / Q000235:genetics; D001528:Behcet Syndrome / Q000235:genetics* / Q000276:immunology; D005805:Genes, MHC Class I / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D059949:HLA-B51 Antigen / Q000235:genetics; D006801:Humans; D015778:Minor Histocompatibility Antigens; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000235:genetics; D054389:Receptors, CCR1 / Q000235:genetics; D050797:STAT4 Transcription Factor / Q000235:genetics; D044764:Ubiquitin-Activating Enzymes / Q000235:genetics
chemical_list: C515300:CCR1 protein, human; D059949:HLA-B51 Antigen; C527066:KLRC4 protein, human; D015778:Minor Histocompatibility Antigens; D055654:NK Cell Lectin-Like Receptor Subfamily C; D054389:Receptors, CCR1; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; C470301:UBA2 protein, human; D000626:Aminopeptidases; C464841:ERAP1 protein, human; D044764:Ubiquitin-Activating Enzymes