Genome-wide association analysis of psoriasis patients treated with anti-TNF drugs

Exp Dermatol. 2020 Dec;29(12):1225-1232. doi: 10.1111/exd.14215. Epub 2020 Oct 29.

Abstract

While anti-TNF therapies are effective against psoriasis, 30%-50% of patients do not show an adequate response to these drugs. Different candidate-gene pharmacogenetics studies have identified single nucleotide polymorphisms that may predict anti-TNF drugs response in psoriasis. Nevertheless, only one paper has undertaken a pharmacogenomic approach failing to find significant biomarkers of biological drug response along the whole genome. Furthermore, most of the pharmacogenetic candidate biomarkers identified previously have not been confirmed in a different cohort of patients. The objective of this study was to find biomarkers that could predict anti-TNF drugs response along the whole genome and validate biomarkers identified previously. A genome-wide association study (GWAS) was performed using the Human Omni Express-8 v1.2 Beadchips in 243 psoriasis patients treated with anti-TNF drugs. This study was multicentric and did not interfere with clinical practice. Associations between single nucleotide polymorphisms (SNP) and PASI75 (a 75% reduction with respect to baseline PASI) at 3 months were evaluated. Imputation was performed using SNPs with R2 > 0.7. There were two SNPs located in NPFFR2 that were close to the significant threshold of 5 × 10-8 . These data suggest that NPFFR2 might be associated with anti-TNF drug response. However, further studies involving a larger cohort of patients are needed in order to confirm these results.

Keywords: biological drugs; biomarkers; microarray; pharmacogenetics; pharmacogenomics; psoriasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab / therapeutic use
  • Adult
  • Biomarkers, Pharmacological
  • Dermatologic Agents / therapeutic use*
  • Etanercept / therapeutic use
  • Female
  • Genome-Wide Association Study
  • Humans
  • Infliximab / therapeutic use
  • Male
  • Middle Aged
  • Pharmacogenomic Testing
  • Polymorphism, Single Nucleotide
  • Psoriasis / drug therapy*
  • Psoriasis / genetics*
  • Receptors, Neuropeptide / genetics*
  • Severity of Illness Index
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • Biomarkers, Pharmacological
  • Dermatologic Agents
  • Receptors, Neuropeptide
  • Tumor Necrosis Factor-alpha
  • neuropeptide FF receptor
  • Infliximab
  • Adalimumab
  • Etanercept