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

Pharmacogenomics J. 2015 Aug;15(4):322-5. doi: 10.1038/tpj.2014.71. Epub 2014 Nov 18.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / genetics
  • Cohort Studies
  • Cyclic Nucleotide Phosphodiesterases, Type 3 / genetics*
  • Endpoint Determination
  • Female
  • Genetic Variation
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Organic Anion Transporters / genetics*
  • Polymorphism, Single Nucleotide
  • Psoriasis / drug therapy*
  • Psoriasis / genetics*
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Antirheumatic Agents
  • Organic Anion Transporters
  • SLCO1C1 protein, human
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • Cyclic Nucleotide Phosphodiesterases, Type 3
  • PDE3A protein, human