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.

• Authors: Isabel Acosta-Colman, Núria Palau, Jesús Tornero, Antonio Fernández-Nebro, Francisco Blanco, Isidoro González-Alvaro, Juan D Cañete, Joan Maymó, Javier Ballina, Benjamín Fernández-Gutiérrez, Alex Olivé, Héctor Corominas, Alba Erra, Oriol Canela-Xandri, Arnald Alonso, Maria López Lasanta, Raül Tortosa, Antonio Julià, Sara Marsal
• Journal: Pharmacogenomics (Pharmacogenomics) Vol. 14 Issue 7 Pg. 727-34 (May 2013) ISSN: 1744-8042 [Electronic] England
• PMID: 23651021 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• Antirheumatic Agents (therapeutic use)
• Arthritis, Rheumatoid (drug therapy, 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)