Genetics of Psoriatic Arthritis – an update

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Darren D. O'Rielly Proton Rahman


Psoriatic arthritis (PsA) is an inflammatory arthritis that commonly occurs with psoriasis and is attributed to genetic, immunologic and environmental factors. It shares skin involvement with psoriasis, articular involvement particularly with spondyloarthritis, bowel involvement with Crohn’s disease and eye involvement with uveitis, suggesting the existence of some common pathways. The Th-17 pathway and the IL-23/IL-17 axis have become prominent players in PsA and have considerably increased our understanding of disease pathogenesis. In this review article, we will focus on the genetic, epigenetic, and pharmacogenetic information with respect to PsA. Prominent genes identified in PsA via GWAS include HLA-A, HLA-B, HLA-C, IL-12B, IL-23R, IL-23A, TNIP1, TRAF3IP2, CSF2/P4HA2, FBXL19, REL, TYK2, NOS2, PTPN22, TNFAIP3, IFNLR1, IFIH1, and NFKBIA. These genetic markers have also illuminated key signaling pathways involved in PsA pathogenesis which can be broadly classified into those involved in epidermal differentiation, innate immunity, antigen presentation and processing, and acquired/adaptive immunity. With respect to PsA pathogenesis, the most consistent and predominant genetic effect is located on chromosome 6p21.3 within the major histocompatibility complex (MHC) region. The most significant association for increased PsA risk was with asparagine or serine residue at amino acid position 97 of HLA-B, where asparagine at position 97 of HLA-B represents the HLA-B*27 allele. Moreover, specific HLA alleles have been associated with disease susceptibility, expression and progression in PsA. The prominent emerging role of the Th-17 signaling pathway in PsA pathogenesis will be highlighted. The lack of identified PsA genetic susceptibility loci is largely attributed to the much smaller number of patients, classification criteria used, and the greater clinical heterogeneity of PsA compared with psoriasis.

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O'RIELLY, Darren D.; RAHMAN, Proton. Genetics of Psoriatic Arthritis – an update. Medical Research Archives, [S.l.], v. 6, n. 3, mar. 2018. ISSN 2375-1924. Available at: <>. Date accessed: 21 apr. 2018. doi:
Review Articles


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