Genetics of Behçet's disease: lessons learned from genomewide association studies

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.

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.

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.