|●抄 録 ：
○Motohiko Tanino1, Ryo Matoba1, Seiji Nakamura1, Hideto Kameda2, Koichi Amano3, Toshitsugu Okayama4, Hayato Nagasawa3, Katsuya Suzuki3, Kenichi Matsubara1, and Tsutomu Takeuchi2
- DNA Chip Research Inc.
- Division of Rheumatology Department of Internal Medicine, Keio University School of Medicine
- Department of Rheumatology/Clinical Immunology, Saitama Medical Center, Saitama Medical University
- BITS Co., Ltd.
For the discovery of drug targets of Rheumatoid Arthritis (RA), we first extracted the susceptibility genes with RA and stratified them according to the response of an anchor drug for RA, Methotrexate (MTX), using gene expression profiling of peripheral blood RNAs of DNA microarray technologies. In order to find new targets, we then related those susceptible genes to canonical biological pathways.
A comprehensive transcriptome analysis was done using a commercial chip with peripheral blood RNAs taken from, in total, 30 RA patients who had MTX treatment (paired samples of before and 4 weeks after treatment), and 27 age and sex matching healthy volunteers recruited for this study. RA susceptible genes, differentially expressed between 30 before MTX treatment and 27 healthy individual samples, were selected. MTX susceptible genes were also selected from the 30 paired RA samples (before vs. 4 weeks after). We mapped those genes onto the pathways in MetaCoreTM DB and performed an enrichment analysis.
We extracted 1864 RA susceptible and 444 MTX susceptible genes respectively and found that 55 genes belonged to both categories. Forty two of those 55 genes were up regulated in RA patients comparing with healthy individuals and down regulated after MTX treatment. The pathway analysis revealed that they were related to cell cycle regulators, such as Cyclin B1 and Cyclin-dependent kinase 1, showing that the molecular evidence of the effect of MTX as a cell cycle inhibitor in RA patients. We also stratified the remaining differentially expressed genes to RA susceptible and MTX UNsusceptible category which should includes new drug targets for those who are resistant against MTX.