Association of RETN and TNFRSF1B polymorphisms with TNF-α inhibitor response in rheumatoid arthritis patients

Abstract

Background: Despite the improvement from the introduction of tumor necrosis factor inhibitors (TNFi) in the rheumatoid arthritis (RA), TNFi therapy fails for more than 30% or results in a partial response. Thus, we aimed to explore treatment marker by examining the association of single nucleotide polymorphisms (SNPs) with response to TNFi therapy.Method: Genes associated with RA or RA treatment were reviewed and fourteen SNPs with minor allele frequency ≥ 20% in the East Asian populations were selected and analyzed. Data were collected from 105 RA patients. Our primary endpoint was the disease activity score using 28-joint count after six months of treatment (DAS28-6month). The secondary outcomes were the subcomponents of DAS28.Results: A total of 88 patients were included in the final analyses. Among the 14 SNPs analyzed, one SNP showed statistical significance in DAS28-6month: patients with the GG allele of RETN rs1862513 had a 4.7 times higher chance of low disease activity at 6-months than GC or CC-carriers (p = 0.033), as indicated by multivariable logistic regression analysis. Rs3397 was marginally significant in univariate analysis (p=0.059), but was significant in the multivariable model (p=0.041). The final model explained 24.5% (Nagelkerke R2) of the variance in DAS28-6month.Conclusion: Our results demonstrated that, among the genes related to RA, SNPs in RETN and TNFRSF1B were associated with the response of TNFi treatment.