New insights toward the pathogenesis of ankylosing spondylitis; genetic variations and epigenetic modifications

Abstract: Ankylosing spondylitis (AS) is a chronic inflammatory autoimmune disease, characterized by typically an axial arthritis. AS is the prototype of a group of disorders called spondyloarthropathies, which is believed to have common clinical manifestations and genetic predisposition. To date, the exact etiology of AS remains unclear. Over the past few years, however, the role of genetic susceptibility and epigenetic modifications caused through environmental factors have been extensively surveyed with respect to the pathogenesis of AS, resulted in important advances. This review article focuses on the recent advances in the field of AS research, including HLA and non-HLA susceptibility genes identified in genome-wide association studies (GWAS), and aberrant epigenetic modifications of gene loci associated with AS. HLA genes most significantly linked with AS susceptibility include HLA-B27 and its subtypes. Numerous non-HLA genes such as those in ubiquitination, aminopeptidases and MHC class I presentation molecules like ERAP-1 were also reported. Moreover, epigenetic modifications occurred in AS has been summarized. Taken together, the findings presented in this review attempt to explain the circumstance by which both genetic variations and epigenetic modifications are involved in triggering and development of AS. Nonetheless, several unanswered dark sides continue to clog our exhaustive understanding of AS. Future researches in the field of epigenetics should be carried out to extend our vision of AS etiopathogenesis.