Psoriasis Bench to Bedside

New insights into the genetics of psoriasis: where could this lead us?

“…The MHC locus (HLA-Cw6 and other MHC variants), the major locus involved in the immune reactions of human immune disease, has consistently been shown to be associated with psoriasis, both in previous linkage and present GWA studies [4,5,8,9]. IL-12, first discovered in 1989, plays an important role in the cell-mediated immune response.…”

“…Recently, Nair et al performed a GWA study in a Caucasian population and found several immune-related genes, including three genes involved in IL-23 signaling (IL23A, IL23R and IL12B), two genes that act downstream of TNF-α and regulate nuclear factor-kB signaling (TNIP1 and TNFAIP3) and two genes involved in the modulation of Th2 immune responses (IL4 and IL13), which are highly associated with susceptibility to psoriasis [8]. As all genes implicated here are involved in the regulation of immune responses, this, in turn, emphasizes the importance of the immune pathway in the pathogenesis of psoriasis [8].…”

“…Since 2005, over 700 genes for more than 100 common diseases and traits have been identified by GWA [101], including those in inflammatory bowel disease, Type 2 diabetes and breast cancer, which sets a solid foundation for further study to explore disease pathogenesis [7]. Recently, three GWA studies on psoriasis published in Nature Genetics have provided us with many novel clues concerning disease pathogenesis, in both immune and non immune pathways [8,9].…”

Paradoxical adverse effects of anti-TNF-α treatment: onset or exacerbation of cutaneous disorders

“…The epidemiology of psoriasis is consistent with it being a polygenic disease, where multiple genes with small effects interact with one another and with the environment to determine psoriasis susceptibility and response to treatment. Recent large-scale genome-wide association studies have yielded new candidate genes encoding molecules involved in the immune response, such as HLA-C, cytokines, NF-κB pathway proteins and β-defensins, and those in the epidermal differentiation complex with functional relevance to psoriasis [76][77][78][79]. The identification and the knowledge of these factors will allow us to target patients with specific drugs and will assist in the decision-making process regarding choice of biological agents.…”

Biomarkers for Comorbidities in Psoriasis: A Report from the Grappa 2011 Annual Meeting

“…Recent genome-wide association studies (GWAS) identified genes that are common to both psoriasis and PsA, as well as some genes that are differentially expressed in the 2 conditions 11 . HLA-C and IL-23 were associated more strongly with psoriasis than PsA, and IL-12B was more strongly associated with PsA.…”