GWAS Replication Study Confirms the Association of PDE3A–SLCO1C1 with anti-TNF Therapy Response in Rheumatoid Arthritis

Abstract

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.

Original submitted 9 January 2013; Revision submitted 13 March 2013

KEYWORDS::

• anti-TNF therapy
• biomarker
• EULAR response
• genetic predictor
• rheumatoid arthritis
• single nucleotide polymorphism

Financial & competing interests disclosure

This work was supported by the Spanish Ministry of Economy and Competitiveness Project grants (PSE-010000-2006-6, IPT-010000-2010-36). The sponsors had no role in the design or conduct of the study, in the collection, analysis and interpretation of data or in the preparation, review or approval of the manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was supported by the Spanish Ministry of Economy and Competitiveness Project grants (PSE-010000-2006-6, IPT-010000-2010-36). The sponsors had no role in the design or conduct of the study, in the collection, analysis and interpretation of data or in the preparation, review or approval of the manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.