TGF beta1 polymorphisms are candidate predictors of the clinical response to rituximab in rheumatoid arthritis
Résumé
Objective: To evaluate the association between several candidate single-nucleotide polymorphisms (SNPs) and responsiveness to rituximab in patients with rheumatoid arthritis (RA). Methods: Sixty-three RA patients were included. Nine genes (13 SNPs) were subsequently analyzed, including those coding for cytokines involved in synovitis (IL10, LTA, TGF beta 1, TNF-alpha, TNF receptor II) and genes associated with RA susceptibility (-C5 TRAF1, STAT4, TNFAIP3 and PTPN22). Results: Forty-four patients were defined as responders and 19 as nonresponders. TGF beta 1 Codon 10 and TGF beta 1 Codon 25 SNPs were both associated with clinical response (probability to respond to treatment with the Codon 10 C/T genotype: OR = 1.6; P = 0.002, and with the Codon 25 G/C genotype: OR = 1.6; P = 0.025). The probability to be a responder when the TGF beta Codon10 C/T and TGF beta Codon 25 G/C genotypes were co-inherited, doubled (OR = 2.6; P = 0.008). Conclusion: The TGF beta 1 SNPs are associated with a good response to rituximab therapy and as such could be useful genetic biomarkers in predicting therapy outcome. (C) 2011 Societe francaise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.