BackgroundTocilizumab (TCZ) is a humanised monoclonal antibody inhibitor of interleukin-6 receptor, indicated in combination with methotrexate in the treatment of rheumatoid arthritis (RA) in patients with inadequate response or intolerance to prior therapy.PurposeThe aim of our study was to explore the potential role of KCNMB1 genetic polymorphisms as a predictor of tocilizumab efficacy in RA patients.Material and methodsThe KCNMB1 (A >G) (rs703505) genetic variant was genotyped using predesigned TaqMan genotyping assay technology and analysed on a ViiA7 real time PCR system. Clinical response was evaluated at 24 weeks with the use of the 28 joint disease activity score criteria (DAS28). Clinical response was evaluated at 14 weeks using DAS28 and good response and remission were classified according to EULAR criteria. EULAR good response was defined as a change in DAS28 >1.2 and DAS28 ≤3.2. EULAR remission was defined as DAS28 ≤2.6 at 14 weeks. Statistical analysis was performed using SPSS v.20.ResultsClinical data for 140 tocilizumab treated patients were obtained. Patients were aged (mean±SD) 53.25 ± 12.42 years; 79% were female. Mean DAS28 at baseline was 5.71 ± 1.13. KCNMB1-GG genetic polymorphism was associated with EULAR good response (GG vs no GG p = 0.26, OR=0.37, 95% CI 0.14 to 0.93) and with EULAR remission (p = 0.01, OR=0.29, 95% CI 0.09 to 0.87).ConclusionOur results confirm that KCNMB1 (A >G) rs703505 polymorphisms could be useful as a genetic marker of tocilizumab efficacy in RA patients. More studies are necessary to confirm these results.No conflict of interest.
BackgroundInterleukin (IL)-6 is involved in the pathogenesis of rheumatoid arthritis (RA) via its broad effects on immune and inflammatory responses. Sustained IL-6 activity can cause tissue damage in different tissues. Previous studies have shown that G allele at the -174G >C (rs1800795) polymorphism is related to high producing IL-6.PurposeThe aim of our study was to explore the potential role of IL-6 genetic polymorphisms as a predictor of tocilizumab efficacy in RA patients and to compare the results with a previous GWAS.Material and methodsThe IL-6 (G >C) (rs1800795) genetic variant was genotyped using predesigned TaqMan genotyping assay technology and analysed on a ViiA7 real time PCR system. Clinical response was evaluated at 24 weeks with the use of the 28 joint disease activity score criteria (DAS28) and good response and remission were classified according to EULAR criteria. EULAR good response was defined as a change in DAS28 >1.2 and DAS28 ≤3.2. EULAR remission was defined as DAS28 ≤2.6 at 14 weeks. Statistical analysis was performed using SPSS v.20ResultsClinical data for 140 tocilizumab treated patients were obtained. The patients were aged (mean±SD) 53.25 ± 12.42 years; 79% were female. Mean DAS28 at baseline was 5.71 ± 1.13. The IL-6 G >C genetic polymorphisms were not significantly associated with a good EULAR response (CC vs no CC p = 0.35, OR=1.07, 95% CI 0.05 to 19.7; GC vs no GC p = 0.97, OR=1.03, 95% CI 0.22 to 4.70; GG vs no GG p = 0.50, OR=0.58, 95% CI 0.12 to 2.67), or remission (CC vs no CC p = 0.85, OR=1.11, 95% CI 0.41 to 2.98; GC vs no GC p = 0.98, OR=1.01, 95% CI 0.52 to 1.94; GG vs no GG p = 0.88, OR=0.96, 95% CI 0.48 to 1.89).ConclusionOur results confirm that IL-6 G >C rs 1800795 polymorphisms are not useful as a genetic marker of tocilizumab efficacy in RA patients. More studies are necessary to confirm these results.No conflict of interest.
Background Candidate gene association studies have consistently demonstrated that the dysregulation of the immune responses underlying rheumatoid arthritis (RA) are influenced by single nucleotide polymorphisms (SNPs) in immuno-modulating genes. Objectives The aim of this study was to test whether 50 potentially functional SNPs in 17 immuno-modulating genes (IL4, IL4R, IL5, IL8, IL8RA, IL8RB, IL10, IL10RA, IL12A, IL12B, IL13, IL16, IFNG, IFNGR2, CCR5, MIF, and VEGFA) are associated with the risk of RA. Methods We genotyped selected SNPs in 1239 RA patients and 1229 controls using KASPar® assays (LGC Genomics). Five percent of samples were included as quality control duplicates. Results We found that carriers of the IL4 rs2070874T, IL4 rs2243290A, IL4 rs2243250T and IL4 rs2243268C alleles and the IL8RB rs2230054C/C and IL8RB rs1126580G/G genotypes had a significantly increased risk of RA (OR=1.37, 95%CI 1.11-1.71, P=0.004; OR=1.33, 95%CI 1.07-1.65, P=0.009; OR=1.32, 95%CI 1.07-1.63, P=0.01; OR=1.25, 95%CI 1.01-1.56, P=0.04; OR=1.31, 95%CI 1.05-1.63, P=0.01 and OR=1.36, 95%CI 1.10-1.69, P=0.002, respectively) whereas carriers of the IL10 rs3024509C/C genotype showed a significantly decreased risk for the disease (OR=0.26, 95%CI 0.09-0.75, P=0.007). Haplotype analysis also revealed that carriers of the IL4 TTCAT and IL8RB CG haplotypes had a significantly increased risk of RA (OR=1.28, 95%CI 1.05-1.56, P=0.016 and OR=1.24, 95%CI 1.09-1.41, P=0.001, respectively) whereas carriers of the IL4R GG haplotype had a decreased risk of developing the disease (OR=0.78, 95%CI 0.63-0-95, P=0.016). Interestingly, the association of the IL4 rs2243250 polymorphism was confirmed in a well-powered meta-analysis including 7150 individuals (OR=1.186, 95%CI 1.07-1.31, P=0.0010) although we failed to show a relationship between this promoter variant and the expression levels of IL4 mRNA (P=0.51). Finally, SNP-SNP interaction analysis suggested that the IL8RB rs1126580 and IL8RB rs2230054 SNPs also influence on risk of RA through interactions with the CCR5 rs2734648 SNP (P=0.028 and 0.026, respectively). Conclusions These findings strongly suggest that genetic variants within IL4, IL8RB and IL4R genes may play a role in determining the risk for RA. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.5176
BackgroundThe engagement of FcGRs by TNF antagonists could affect macrophage mediated clearance of immune complexes.PurposeThe aim of our study was to explore the potential role of FcGR2A genetic polymorphism as a predictor of tocilizumab efficacy in rheumatoid arthritis (RA) patients.Material and methodsThe FcGR2A (A >G) (rs1801274) genetic variant was genotyped using predesigned TaqMan genotyping assay technology and analysed on a ViiA7 real time PCR system. Clinical response was evaluated at 24 weeks with the use of the 28 joint disease activity score criteria (DAS28). The endpoint was a change in DAS28 (cDAS28). Statistical analysis was performed using SPSS v.20ResultsClinical data for 140 tocilizumab treated patients were obtained. The patients were aged (mean±SD) 53.25 ± 12.42 years; 79% were female. Mean DAS28 at baseline was 5.71 ± 1.13. The FcGR2A-AA polymorphism was significantly associated with cDAS28 (AA vs no AA p = 0.01, OR=0.14, 95% CI 0.02 to 0.81; AG vs no AG p = 0.007, OR=9.52, 95% CI 1.80–14.70).ConclusionOur results confirm that FcGR2A (A >G) rs1801274 polymorphisms could be useful as a genetic marker of tocilizumab efficacy in RA patients. More studies are necessary to confirm these results.No conflict of interest.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.