Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/genetics , Receptors, Tumor Necrosis Factor, Type II/genetics , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adult , Aged , Aged, 80 and over , Arthritis, Rheumatoid/immunology , Humans , Male , Middle Aged , Peptides, Cyclic/immunology , Polymorphism, Genetic , Predictive Value of Tests , Receptors, Tumor Necrosis Factor, Type II/immunology , Young AdultABSTRACT
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, TGFß1, TNF-α, 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. TGFß1 Codon 10 and TGFß1 Codon 25 SNPs were both associated with clinical response (probability to respond to treatment with the Codon 10C/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 TGFß Codon10 C/T and TGFß Codon 25 G/C genotypes were co-inherited, doubled (OR = 2.6; P = 0.008). CONCLUSION: The TGFß1 SNPs are associated with a good response to rituximab therapy and as such could be useful genetic biomarkers in predicting therapy outcome.
