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A Long and Winding Road Ahead in Personalized Medicine

Genetics research shows great promise for personalized treatment in rheumatology - but diagnostic and prognostic gene tests are years away.

Recent advances in rheumatoid arthritis (RA) genetics research show great promise for the future personalization of treatment-but diagnostic and prognostic gene tests are probably still several years away from clinical validation, regulatory approval and routine use, cautioned authors of a review published in Gene.

Gene tests for rheumatoid arthritis face a “long and winding road” to FDA approval and widespread adoption, they concluded. Despite impressive advances in the study of rheumatoid arthritis genetics and gene/drug interactions, and the growing availability of rapid gene-sequencing technologies like Next Generation Sequencing, the use of gene tests for rheumatoid arthritis will likely continue to lag behind clinical oncology, they wrote.

Progress is being made at an “astonishing” rate, but much has yet to be discovered about the genetic underpinnings of rheumatoid arthritis, they wrote. Genome-wide association studies have identified more than 100 candidate rheumatoid arthritis-susceptibility genes to date, many of them involved in T-cell activation and signaling gene pathways. “Somewhat surprisingly, these susceptibility loci account for less than 50% of the total genetic heritability [of rheumatoid arthritis], suggesting that there is a significant portion of the genetic architecture of RA that remains to be discovered,” they wrote.  [[{"type":"media","view_mode":"media_crop","fid":"47602","attributes":{"alt":"©Watchara/Shutterstock.com","class":"media-image media-image-right","id":"media_crop_9829038905157","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"5621","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.008px; line-height: 1.538em; float: right;","title":"©Watchara/Shutterstock.com","typeof":"foaf:Image"}}]]

Risk genes could one day help with early detection and treatment decisions for patients. However, the genes thus far identified each play a small role in a patient’s overall rheumatoid arthritis risk, meaning that when gene tests are developed, they will likely be panel tests that assess numerous genes at one time.

“While these applications are largely not refined to the point of clinical utility in RA, it seems likely that multi-parameter datasets including genetic, clinical, and biomarker data will be employed in the future care of RA patients,” wrote lead study author George N. Goulielmos, M.D., of the Laboratory of Molecular Medicine and Human Genetics, Medical School of Crete, in Greece, and co-authors from the University of Leeds in England and the Mayo Clinic in Rochester, Minnesota.

“In RA, although there is not yet any guidance about which treatment will be the most suitable for any particular patient, it seems likely that genetic variation will be useful in predicting treatment response,” the authors wrote.

Advances in other areas-including RNA, protein, and epigenetic testing--might also yield new tools for the early identification of rheumatoid arthritis phenotypes, they wrote. For example, recent epigenetics research has tied epigenetic modifications to an aggressive, intrinsically activated form of rheumatoid arthritis, the researchers wrote. “Linking genetic and epigenetic data with gene expression and proteomics/metabolics is certainly the biggest challenge we are facing, and novel tools need to be developed to this end.”




Goulielmos GN, Zervou MI, Myrthianou E, et al. "Genetic data: the new challenge of personalized medicine, insights for rheumatoid arthritis patients." Gene2016;583:90-101.