Association of the PDE3A-SLCO1C1 locus with the response to anti-TNF agents in psoriasis

Abstract

Psoriasis is a prevalent autoimmune disease of the skin that causes significant psychological and physical disability. Tumor necrosis factor (TNF)-blocking agents have proven to be highly efficacious in the management of moderate-to-severe psoriasis. However, a significant percentage of patients do not respond to this treatment. Recently, variation at the PDE3A-SLCO1C1 (phosphodiesterase 3A-SoLute Carrier Organic anion transporter family member 1C1) locus has been robustly associated with anti-TNF response in rheumatoid arthritis. Using a cohort of 130 psoriasis patients treated with anti-TNF therapy, we sought to analyze the association of this locus with treatment response in psoriasis. We found a highly significant association between PDE3A-SLCO1C1 and the clinical response to TNF blockers (P=0.0031). Importantly, the allele that was previously associated with the lack of response to rheumatoid arthritis (G allele, single-nucleotide polymorphism rs3794271) was associated with a higher anti-TNF efficacy in psoriasis. The results of this study are an important step in the characterization of the pharmacogenetic profile associated with anti-TNF response in psoriasis.

Associations between functional polymorphisms and response to biological treatment in Danish patients with psoriasis

“…[33][34][35][36][37][38][39][40][41][42][43] For all significant associations, except TLR9 (rs352139) and LY96 (rs11465996), similar tendencies were observed for ORs for each of the anti-TNF agents (data available on request). To our knowledge, this is one of the largest cohorts for evaluation of response in patients treated with ustekinumab 44,45 and the second largest for evaluation of anti-TNF; only a Canadian study (also involving treatment primarily for psoriatic arthritis) had more patients.…”

A systematic review of pharmacogenetic studies on the response to biologics in patients with psoriasis

“…Patients who were homozygous for the LCE3B/3C deletion, another known risk variant for psoriasis, had a less favourable response to anti‐TNF agents . Pharmacogenetic associations were also reported for genetic variants in the following susceptibility genes: CARD14 , CDKAL1 , FCGR3A and PDE3A‐SLCO1C1 (File S6; see Supporting Infromation) …”

“…Five studies investigated pharmacogenetics for adalimumab . Contrary to TNF inhibitors as a group, none of the SNPs in TNF‐α‐related genes were significantly associated with a response to adalimumab individually.…”

Pharmacogenetics of Psoriasis Treatment

“…FCGR3A rs396991 was also evaluated by Mendrinou et al who showed that T allele could be a marker of beter response to etanercept [58]. Moreover, a positive association was found between PDE3A-SLCO1C1 rs3794271AA genotype and PASI score in patients treated with etanercept [59]. Association between the CD84 genotypes and response to biologics was also evaluated.…”