Methods: We included 508 TNFi treated RA patients. Association analysis of change of visual analogue scale of pain (VAS-pain) after 14 weeks of treatment was performed on imputed genome-wide genotyping data under additive genetic model with adjustment for baseline VAS-pain. We alsoconducted a meta-analysis including 1287 RA patients. Gene-based analysis was performed using VEGAS.
Results: No findings reached the threshold for genome-wide significance (P-value 1X10-8) in the discovery cohort. Meta-analysis revealed 213 SNPs suggestively associated (P 10-4) with change in VAS-pain after fourteen weeks of TNFi treatment. The most significant SNP rs2295739 (p 2.21X10-6), located 50kb upstream from the KCNK10 gene. Which belongs to a family of genes involved in sensory perception. The top hit in the gene-based analysis was RET, known to regulate ion channels and receptors participating in detection and transduction of sensory stimuli. Besides Ret-deficient mice show elevated pain responses.
Conclusion: We have identified several suggestive genomic regions, further studies are required to validate if these regions play a role in pain reduction upon TNFi treatment.
|Number of pages||1|
|Journal||Arthritis & rheumatology|
|Publication status||Published - 2014|
|Event||ACR/AHRP Annual Scientific Meeting 2014 - Boston Convention Center, Boston, United States|
Duration: 15 Nov 2014 → 19 Nov 2014