Genetic Influence on Treatment Response in Psoriasis: New Insights into Personalized Medicine

Abstract

Psoriasis is a chronic inflammatory disease with an established genetic background. The HLA-Cw*06 allele and different polymorphisms in genes involved in inflammatory responses and keratinocyte proliferation have been associated with the development of the disease. Despite the effectiveness and safety of psoriasis treatment, a significant percentage of patients still do not achieve adequate disease control. Pharmacogenetic and pharmacogenomic studies on how genetic variations affect drug efficacy and toxicity could provide important clues in this respect. This comprehensive review assessed the available evidence for the role that those different genetic variations may play in the response to psoriasis treatment. One hundred fourteen articles were included in this qualitative synthesis. VDR gene polymorphisms may influence the response to topical vitamin D analogs and phototherapy. Variations affecting the ABC transporter seem to play a role in methotrexate and cyclosporine outcomes. Several single-nucleotide polymorphisms affecting different genes are involved with anti-TNF-α response modulation (TNF-α, TNFRSF1A, TNFRSF1B, TNFAIP3, FCGR2A, FCGR3A, IL-17F, IL-17R, and IL-23R, among others) with conflicting results. HLA-Cw*06 has been the most extensively studied allele, although it has only been robustly related to the response to ustekinumab. However, further research is needed to firmly establish the usefulness of these genetic biomarkers in clinical practice.

PDE4 Gene Family Variants Are Associated with Response to Apremilast Treatment in Psoriasis

“…In order to evaluate the identified associations (listed in Table 2 , Table 3 and Table 4 ) and their potential clinical application, we explored the literature for previous associations with autoimmune diseases or diseases with an autoimmune component. Indeed, previous studies have shown that SNPs associated with the response to Ps treatment are also associated with Ps susceptibility [ 27 , 28 ]. Specifically, rs892085 and rs322151, located downstream of PDE4A , have been associated with Ps and PsA [ 29 , 30 , 31 ] and systemic sclerosis, respectively [ 32 ].…”

Functional Genomics and Insights into the Pathogenesis and Treatment of Psoriasis

“…With response to biologic drugs typically being heterogenous, one hypothesis is that this response reflects genetic variance between patients or genetically distinct disease subsets with distinct pathogeneses. The effect of genetics on anti-TNF response is well characterized, with TNF-α, TNFRSF1A, TNFRSF1B, TNFAIP3, FCGR2A, FCGR3A, IL-17F, IL-17R, and IL-23R suggested to modulate response [126], however, few studies explore the interaction of IL-17 and IL-23 inhibitors with genetics. Ustekinumab shows a higher efficacy and faster response time in HLA-Cw*06 positive patients than in negative patients [126], and Van den Reek et al found that the IL12B rs3213094-T allele increased efficacy and TNFAIP3 rs610604-G allele predicting a worse outcome [127], however other studies were unable to replicate this.…”

“…The effect of genetics on anti-TNF response is well characterized, with TNF-α, TNFRSF1A, TNFRSF1B, TNFAIP3, FCGR2A, FCGR3A, IL-17F, IL-17R, and IL-23R suggested to modulate response [126], however, few studies explore the interaction of IL-17 and IL-23 inhibitors with genetics. Ustekinumab shows a higher efficacy and faster response time in HLA-Cw*06 positive patients than in negative patients [126], and Van den Reek et al found that the IL12B rs3213094-T allele increased efficacy and TNFAIP3 rs610604-G allele predicting a worse outcome [127], however other studies were unable to replicate this. The SUPREME study found that HLA-Cw*06 status did not influence response to secuk-inumab [128], however the two Italian studies predicted a higher PASI90 in HLA-Cw*06 positive patients [129,130].…”

Polymorphisms of PDCD1 and COL9A1 Genes in Plaque, Palmoplantar and Arthropathic Psoriasis in Romanian Patients

“…Research focused on pharmacogenetics, pharmacogenomics, and the impact of genetic variations on drug efficacy and adverse reactions could provide valuable insights in this context. Although studies are variable, it appears that genetic variations in the Vitamin D Receptor (VDR) gene might have a link to treatment response involving calcipotriol or other vitamin D analogs among people with psoriasis [9]. Associations between increased minor allele frequency distribution with better apremilast therapy outcomes were found for SNPs located at IL1β, IL4, IL23R, Tumour Necrosis Factor alpha (TNFα) [10].…”