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Rheumatology (Oxford). 2016 Feb;55(2):199-209. doi: 10.1093/rheumatology/keu323. Epub 2014 Sep 18.

The genetics of rheumatoid arthritis: risk and protection in different stages of the evolution of RA.

Author information

1
Arthritis Research UK Centre for Genetics and Genomics, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, Stopford Building, University of Manchester, Manchester, UK.
2
Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands and.
3
Arthritis Research UK Centre for Genetics and Genomics, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, Stopford Building, University of Manchester, Manchester, UK, NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK jane.worthington@manchester.ac.uk.

Abstract

There is now a general consensus that RA has a spectrum of disease stages that can begin many years before the onset of clinical symptoms. It is widely thought that understanding the complex interplay between genetics and environment, and their role in pathogenesis, is essential in gaining further insight into the mechanisms that drive disease development and progression. More than 100 genetic susceptibility loci have now been identified for RA through studies that have focused on patients with established RA compared with healthy controls. Studying the early preclinical phases of disease will provide valuable insights into the biological events that precede disease and could potentially identify biomarkers to predict disease onset and future therapeutic targets. In this review we will cover recent advances in the knowledge of genetic and environmental risk factors and speculate on how these factors may influence the transition from one stage of disease to another.

KEYWORDS:

anti-carbamylated autoantibodies; anti-citrullinated autoantibodies; autoantibodies; disease phase; environment; genetics; inflammatory polyarthritis; rheumatoid arthritis; risk prediction; undifferentiated arthritis

PMID:
25239882
PMCID:
PMC4710800
DOI:
10.1093/rheumatology/keu323
[Indexed for MEDLINE]
Free PMC Article

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