A polymorphism in the gene encoding the Fcgamma IIIA receptor is a possible genetic marker to predict the primary response to infliximab in Japanese patients with rheumatoid arthritis

摘要

The prediction of treatment outcome of patients with rheumatoid arthritis (RA) may avoid wasting time and cost of treatment, and allow better targeting of aggressive treatment. Recently, an amino acid-changing polymorphism in the gene encoding the Fcgamma IIIA receptor (FcgammaRIIIA), valine (V)/phenylalanine (F) (rs396991), was found to be associated with increased likelihood of response to tumour necrosis factor (TNF)-alpha inhibitors in the treatment of RA. The aim of the present study was to determine whether this FcgammaRIIIA V/F polymorphism is associated with treatment outcome of infliximab (the first TNF-alpha inhibitor approved in Japan) in Japanese patients with RA.The study was approved by the Tokyo Women's Medical University Genome Ethics Committee. The basis of this study was the collection of prospective clinical data from Japanesepatients with RA who had received infliximab. The diagnosis of RA was established using the American College of Rheumatology 1987 revised classification criteria. All clinical data to calculate the disease activity score (DAS28) werecollected at weeks 0, 2 and 6, and every 8 weeks thereafter. The reasons for cessation of treatment with infliximab were also recorded. Each patient was categorised as being a good or moderate responder (responder), or a non-responder according to EULAR response criteria at 22 weeks. DNA samples were obtained from 33 patients who were naive to TNF-alpha inhibitors when treatment with infliximab was started. The genotyping of rs396991 was performed using the TaqMan assay according to the manufacturer's instructions (Applied Biosystems, Tokyo, Japan). A genotype comparison was performed with a 2x3 table and calculation of Fisher's exact test, which were implemented in the R software package (version 2.6.0, http://www.r-project.org/).