title: Functional Genomics and Its Bench-to-Bedside Translation Pertaining to the Identified Susceptibility Alleles and Loci in Ankylosing Spondylitis.
abstract: Ankylosing spondylitis (AS) is a highly heritable disease for which there is a great unmet need for improved therapies. Genetics research has identified several major pathways involved in the disease, from which treatments have either now entered clinical practice or are in development. In particular, therapies targeting the IL-23 pathway were repositioned for use in AS following the discovery of multiple genes in the pathway as determinants of AS risk. Discovery of the association of aminopeptidase genes with AS, and subsequently with psoriasis, inflammatory bowel disease and other conditions, has triggered research into therapies targeting this pathway. The AS-genetic associations point to involvement of gut mucosal immunity in driving disease, and metagenomic studies have provided strong support that AS is a disease driven by interaction between the gut microbiome and host immune system, providing a rationale for the exploration of gut-targeted therapies for the disease.
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Princess Alexandra Hospital, Woolloongabba, Brisbane, QLD, 4102, Australia.
authors.forename: Tony J
authors.initials: TJ
authors.lastname: Kenna
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Princess Alexandra Hospital, Woolloongabba, Brisbane, QLD, 4102, Australia.|University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Woolloongabba, Brisbane, QLD, 4102, Australia.
authors.forename: Aimee
authors.initials: A
authors.lastname: Hanson
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Princess Alexandra Hospital, Woolloongabba, Brisbane, QLD, 4102, Australia.
authors.forename: Mary-Ellen
authors.initials: ME
authors.lastname: Costello
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Princess Alexandra Hospital, Woolloongabba, Brisbane, QLD, 4102, Australia. Matt.brown@qut.edu.au.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Brown
mesh_terms: D000483:Alleles; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D023281:Genomics; D006801:Humans; D013167:Spondylitis, Ankylosing / Q000235:genetics*
keywords: Aminopeptidase; Ankylosing spondylitis; Functional genomics; Genetics; IL-23; Microbiome; Single nucleotide polymorphism