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.
Aim: This study aimed to examine the effects of polymorphisms in nuclear factor of activated T cells C2 (NFATC2), a TNF-α transcription factor, on remission in RA patients receiving TNF-α inhibitors. Methods: This prospective observational study was performed in two centers. Nine single nucleotide polymorphisms (SNPs) were investigated, and haplotype analyses were performed. Logistic regression analyses were used to investigate the association between genetic polymorphisms and remission of RA. Results: This study included 88 patients, among whom 26 had remission of RA. We identified a haplotype, H2 (CCT), which carried 3 NFATC2 SNPs (rs1052649, rs1569736, and rs763944) and showed a significant relationship with remission. After adjusting for covariates, H2 carriers exhibited approximately 2.86-fold higher rates of remission than others (p=0.049). In subgroup analysis with patients with the TT genotype of rs1799964 of TNF-α, patients with the CC genotype in NFATC2 rs763944 showed an approximately 4.1-fold lower remission rate than T-allele carriers (p = 0.028), after adjusting for related covariates. In another subgroup analysis among patients with the GG genotype of TNF-α rs361525, patients with the CC genotype in NFATC2 rs763944 showed an approximately 3.2-fold lower remission rate than T-allele carriers (p = 0.04) after adjusting for covariates. Conclusion: This study suggested an association between NFATC2 polymorphisms and remission in RA patients receiving TNF-α inhibitors.
Objectives Nuclear factor of activated T cells C2 (NFATC2) is known as a member of the transcription family and enhances tumor necrosis factor-alpha (TNFα) synthesis in human T cells at the gene transcription level. Although NFATC2 has a potential role in rheumatoid arthritis (RA) progression and treatment, no study has investigated the association between NFATC2 gene polymorphisms and response status in RA patients receiving TNF-α inhibitors. This study aimed to examine the effects of polymorphisms in NFATC2, a TNF-α transcription factor, on response to TNF-α inhibitors.Methods This prospective observational study was performed in two centers. Seven single nucleotide polymorphisms (SNPs) were investigated. Good responders were defined as patients with disease activity score (DAS)28 ≤3.2 after 6 months of treatment. Logistic regression analyses were used to investigate the association between genetic polymorphisms and response to the treatment. To test the model's goodness of fit, a Hosmer-Lemeshow test was performed.
ResultsThis study included 98 patients, among whom 46 showed favorable responses to the treatment. Patients with hypertension revealed an approximately three-fold lower response to TNF-α inhibitors compared to those without hypertension (23.5 vs. 76.5%; P = 0.049). After adjusting for covariates, C allele carriers of NFATC2 rs3787186 exhibited approximately three-fold lower rates of treatment response compared to those with TT genotype (P = 0.037). The Hosmer-Lemeshow test showed that the fitness of the multivariable analysis model was satisfactory (χ 2 = 9.745; 8 degrees of freedom; P = 0.283).
ConclusionThis study suggested an association between the C allele of rs3787186 and treatment response in RA patients receiving TNF-α inhibitors.
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