Previously reported PDE3A-SLCO1C1 genetic variant does not correlate with anti-TNF response in a large UK rheumatoid arthritis cohort

Pharmacogenomics. 2016 May;17(7):715-20. doi: 10.2217/pgs.16.16. Epub 2016 May 16.

Abstract

Aim: A genetic variant has recently reached genome-wide significance for association with TNF-inhibitor response in rheumatoid arthritis patients. Here we undertake a replication study in a UK Caucasian population to test for association with TNF-inhibitor response.

Materials & methods: The genetic variant, rs3794271, located within the PDE3A-SLCO1C1 locus was analyzed for correlation with treatment response using both the EULAR classification criteria and absolute change in (Δ)DAS28 scores as outcome measures.

Results: Genotype data were available from 1750 TNF-inhibitor treated individuals. However, no evidence for association was observed (EULAR: p = 0.91 and ΔDAS28: p = 0.93). Furthermore, no significant associations were observed upon stratification by the anti-TNF received (p > 0.05).

Conclusion: In the largest replication cohort conducted to date, no evidence for association was observed.

Keywords: TNF inhibitors; biomarker; rheumatoid arthritis; single nucleotide polymorphism; treatment response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antirheumatic Agents / pharmacokinetics
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / metabolism
  • Cohort Studies
  • Cyclic Nucleotide Phosphodiesterases, Type 3 / genetics*
  • Cyclic Nucleotide Phosphodiesterases, Type 3 / metabolism
  • Female
  • Genetic Association Studies
  • Humans
  • Male
  • Middle Aged
  • Organic Anion Transporters / genetics*
  • Organic Anion Transporters / metabolism
  • Pharmacogenomic Testing
  • Pharmacogenomic Variants*
  • Polymorphism, Single Nucleotide
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • United Kingdom

Substances

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