GWAS replication study confirms the association of PDE3A-SLCO1C1 with anti-TNF therapy response in rheumatoid arthritis

Pharmacogenomics. 2013 May;14(7):727-34. doi: 10.2217/pgs.13.60.


Aim: The present study was undertaken to replicate the association of candidate genes for anti-TNF response in rheumatoid arthritis. Candidate genes were selected from a recent genome-wide association study on anti-TNF response performed in a population from Denmark.

Materials & methods: Genomic DNA was obtained from 315 Spanish rheumatoid arthritis patients having received an anti-TNF agent as their first biological therapy. SNPs from NR2FR2, MAP2K6, CBLN2 and PDE3A-SLCO1C1 candidate loci were genotyped.

Results: The PDE3A-SLCO1C1 locus rs3794271 SNP showed a highly significant association with anti-TNF treatment response (p = 1.74 × 10⁻⁵). Combining the statistical evidence from the Spanish and Danish rheumatoid arthritis cohorts, the associated rs3794271 SNP reached a genome-wide significance level of association (p = 3.3 × 10⁻¹⁰).

Conclusion: The present findings establish the PDE3A-SLCO1C1 locus as a strong genetic marker of anti-TNF therapy response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / genetics*
  • Cyclic Nucleotide Phosphodiesterases, Type 3 / genetics*
  • Denmark
  • Female
  • Genetic Loci
  • Genetic Markers / genetics
  • Genome-Wide Association Study / methods
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Organic Anion Transporters / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


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