Objectives The regulation of cytokine production on the level of the gene transcription may involve several types of polymorphisms in promoter/enhancer region. The aim of this study was to evaluate if polymorphism in several genes could associate with the responsiveness to TNF blocking therapy with etanercept (Enbrel®) in patients with rheumatoid arthritis from Eastern Sweden.
Methods 124 patients with active RA were treated with subcutaneous etanercept 25 mg twice a week. The efficacy measures included ACR and DAS28 response rates after treatment for 3 months. The ?308 TNFA, -1082 IL10 and codon 25 TGFB1 gene polymorphisms were detected by combination of PCR and restriction endonuclease mapping. VNTRs in intron 2 of IL1RN gene were detected by PCR and HLA-DQB1 and HLA-DRB1 were typed and subtyped by PCR-SSP.
Results 24 patients (19%) were non-responders according to both ACR and DAS28 criteria. We found significant association of one group, composite of TNF1/TNF1 and G/G genotypes, with positive responsiveness to etanercept (p < 0.05). Non-responders with TNF2 allele had relatively low ESR before treatment (mean ± SE = 25 ± 5 mm/min) in comparison with other groups (p < 0.05, Fisher’s PLSD). Individuals with non-shared epitope genes showed approximately 2 times more frequent fail of the therapy if ACR criteria was used.
Conclusion We find strong evidence for association of certain genetic markers with efficacy of etanercept treatment in RA patients. Combined ?308 TNFA and ?1082 IL10 genotype may predispose for the response to etanercept therapy, while ?308 TNFA genotype in combination with ESR may be used for the selection of potential non-responders. These results may provide information for future improvement of treatment of RA.
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