TRAF1/C5but NotPTPRCVariants Are Potential Predictors of Rheumatoid Arthritis Response to Anti-Tumor Necrosis Factor Therapy

Abstract

Background. The aim of our work was to replicate, in a Southern European population, the association reported in Northern populations between PTPRC locus and response to anti-tumor necrosis factor (anti-TNF) treatment in rheumatoid arthritis (RA). We also looked at associations between five RA risk alleles and treatment response. Methods. We evaluated associations between anti-TNF treatment responses assessed by DAS28 change and by EULAR response at six months in 383 Portuguese patients. Univariate and multivariate linear and logistic regression analyses were performed. In a second step to confirm our findings, we pooled our population with 265 Spanish patients. Results. No association was found between PTPRC rs10919563 allele and anti-TNF treatment response, neither in Portuguese modeling for several clinical variables nor in the overall population combining Portuguese and Spanish patients. The minor allele for RA susceptibility, rs3761847 SNP in TRAF1/C5 region, was associated with a poor response in linear and logistic univariate and multivariate regression analyses. No association was observed with the other allellic variants. Results were confirmed in the pooled analysis. Conclusion. This study did not replicate the association between PTPRC and the response to anti-TNF treatment in our Southern European population. We found that TRAF1/C5 risk RA variants potentially influence anti-TNF treatment response.

Association of TRAF1/C5 Locus Polymorphisms with Epilepsy and Clinical Traits in Mexican Patients with Neurocysticercosis

“…In previous studies of rheumatoid arthritis, high LD values were found between the TRAF1 and C5 genes, a result that precluded the determination of which of these two genes is responsible for the exacerbated inflammatory response (43). However, an LD of Ͻ78 between both genes was found in our study, a value like that reported by Kurreeman et al for these genes (16).…”

Systematic review and meta-analysis: pharmacogenetics of anti-TNF treatment response in rheumatoid arthritis

“…In total, 47 studies were included in the analysis; 42 candidate gene studies 14 , 15 , 16 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 and 5 genome-wide association studies (GWAS) 60 , 61 , 62 , 63 , 64 analysing responders versus non-responders from anti-TNF therapy in RA ( Table 1 ). Two studies reported associations between polymorphisms and treatment response in juvenile idiopathic arthritis (JIA) 37 , 50 and the others on adult RA.…”

TRAF1 Signaling in Human Health and Disease

“…Increased serum levels of TRAF1 correlate with disease activity and autoantibodies in RA patients. Moreover, SNPs in the TRAF1-C5 locus may predict the clinical response to anti-TNF therapy (79, 80). The expression of TRAF1 is also significantly higher in inflamed and non-inflamed tissues of patients with inflammatory bowel disease compared to those in control patients (81).…”