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Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease that primarily involves the axial skeleton and the sacroiliac joint, but may also affect peripheral joints and entheses. AS susceptibility is clearly attributable to genetic factors and the link between human leukocyte antigen (HLA)‐B27 and AS is the strongest association between an HLA class I molecule and a disease. However, there is evidence for the involvement of other, non‐B27 factors within the major histocompatibility complex (MHC) in AS susceptibility. MHC class I is clearly the most significant genetic region for the disease, although most of the genetic association of this region is driven by HLA‐B27. Moreover, several studies have investigated the MHC class II region and its association with AS. This review summarizes the current findings concerning the MHC genetics of the disease, focusing in particular on the associations of HLA with …