Journal
PHARMACOGENOMICS
Volume 14, Issue 7, Pages 727-734Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/PGS.13.60
Keywords
anti-TNFtherapy; biomarker; EULAR response; genetic predictor; rheumatoid arthritis; single nucleotide polymorphism
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Funding
- Spanish Ministry of Economy and Competitiveness [PSE-010000-2006-6, IPT-010000-2010-36]
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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-INF treatment response (p = 1.74 x 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 x 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
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