Genetics of susceptibility and treatment response in psoriatic arthritis

Psoriatic arthritis (PsA), an inflammatory arthritis associated with psoriasis, has a wide spectrum of disease severity. The clinical heterogeneity in PsA probably reflects substantial genetic heterogeneity. In recent years, many genes that contribute to the pathogenesis of psoriasis and PsA have been identified, especially in Western cohorts. Emerging evidence from functional studies of candidate genes identified by genome-wide association studies is suggestive of an integrated, multi-tiered pathogenic model, comprising distinct signaling networks that affect skin barrier function, innate immune responses (involving NFκB and interferon signaling), and adaptive immune responses (involving CD8(+) T cells and type 17 T-helper-cell signaling). Although several genes--and variants thereof--within these pathways have been associated with susceptibility to psoriasis and PsA, replication in large multiethnic cohorts, fine mapping and resequencing efforts, together with functional studies of the variants, are warranted to better understand their role in disease susceptibility. With respect to pharmacogenetics, several candidate gene polymorphisms have been shown to influence responses to both traditional and biologic therapies in psoriasis and PsA, but confirmation in large prospective cohorts is required before the information can be used in the clinical setting.