Review
Nature Reviews Rheumatology 9, 141-153 (March 2013) | doi:10.1038/nrrheum.2012.237
Focus on: Rational therapy in RA
Genetics and epigenetics of rheumatoid arthritis
Sebastien Viatte, Darren Plant & Soumya Raychaudhuri About the authors
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Abstract
Investigators have made key advances in rheumatoid arthritis (RA) genetics in the past 10 years. Although genetic studies have had limited influence on clinical practice and drug discovery, they are currently generating testable hypotheses to explain disease pathogenesis. Firstly, we review here the major advances in identifying RA genetic susceptibility markers both within and outside of the MHC. Understanding how genetic variants translate into pathogenic mechanisms and ultimately into phenotypes remains a mystery for most of the polymorphisms that confer susceptibility to RA, but functional data are emerging. Interplay between environmental and genetic factors is poorly understood and in need of further investigation. Secondly, we review current knowledge of the role of epigenetics in RA susceptibility. Differences in the epigenome could represent one of the ways in which environmental exposures translate into phenotypic outcomes. The best understood epigenetic phenomena include post-translational histone modifications and DNA methylation events, both of which have critical roles in gene regulation. Epigenetic studies in RA represent a new area of research with the potential to answer unsolved questions.
Author affiliations
S. Viatte, D. Plant & S. Raychaudhuri
Arthritis Research UK Epidemiology Unit, Manchester Academic Health Science Centre, The University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK (S. Viatte). NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK (D. Plant). Divisions of Rheumatology and Genetics, New Research Building (NRB), 77 Avenue Louis Pasteur, Suites 250/255, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA (S. Raychaudhuri).
Correspondence to: S. Raychaudhuri soumya@broadinstitute.org
Published online 5 February 2013
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