Current understanding of the genetic basis of psoriasis

Psoriasis is a common, immunologically mediated, inflammatory and hyperproliferative disease of the skin and joints, with a multifactorial genetic basis. Recently, the association of psoriasis with loci at HLA-Cw*0602, IL12B, IL23A, IL23R, TNFAIP3, TNIP1, ZNF313 and IL4/IL13, and copy number variations in the beta-defensin and late-cornified envelope (LCE) gene loci were described. Here, we discuss the advances in the technology that has lead to the identification of these genes and their presumed role in the pathogenesis of psoriasis. Although it is now generally accepted that psoriatic lesions are caused by abnormal reactivity of specific T cells in the skin, these findings suggest that alterations in the epidermal barrier, innate defenses and processing of inflammatory signals may all contribute to the triggering of nonspecific innate immune mechanisms, which, in combination with altered IL-23 signaling, may lead to the dysregulation of T-cell-driven immune responses.