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Genetics Home Reference: your guide to understanding genetic conditions
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Rheumatoid arthritis

Reviewed September 2013

What is rheumatoid arthritis?

Rheumatoid arthritis is a disease that causes chronic abnormal inflammation, primarily affecting the joints. The most common signs and symptoms are pain, swelling, and stiffness of the joints. Small joints in the hands and feet are involved most often, although larger joints (such as the shoulders, hips, and knees) may become involved later in the disease. Joints are typically affected in a symmetrical pattern; for example, if joints in the hand are affected, both hands tend to be involved. People with rheumatoid arthritis often report that their joint pain and stiffness is worse when getting out of bed in the morning or after a long rest.

Rheumatoid arthritis can also cause inflammation of other tissues and organs, including the eyes, lungs, and blood vessels. Additional signs and symptoms of the condition can include a loss of energy, a low fever, weight loss, and a shortage of red blood cells (anemia). Some affected individuals develop rheumatoid nodules, which are firm lumps of noncancerous tissue that can grow under the skin and elsewhere in the body.

The signs and symptoms of rheumatoid arthritis usually appear in mid- to late adulthood. Many affected people have episodes of symptoms (flares) followed by periods with no symptoms (remissions) for the rest of their lives. In severe cases, affected individuals have continuous health problems related to the disease for many years. The abnormal inflammation can lead to severe joint damage, which limits movement and can cause significant disability.

How common is rheumatoid arthritis?

Rheumatoid arthritis affects about 1.3 million adults in the United States. Worldwide, it is estimated to occur in up to 1 percent of the population. The disease is two to three times more common in women than in men, which may be related to hormonal factors.

What genes are related to rheumatoid arthritis?

Rheumatoid arthritis probably results from a combination of genetic and environmental factors, many of which are unknown.

Rheumatoid arthritis is classified as an autoimmune disorder, one of a large group of conditions that occur when the immune system attacks the body's own tissues and organs. In people with rheumatoid arthritis, the immune system triggers abnormal inflammation in the membrane that lines the joints (the synovium). When the synovium is inflamed, it causes pain, swelling, and stiffness of the joint. In severe cases, the inflammation also affects the bone, cartilage, and other tissues within the joint, causing more serious damage. Abnormal immune reactions also underlie the features of rheumatoid arthritis affecting other parts of the body.

Variations in dozens of genes have been studied as risk factors for rheumatoid arthritis. Most of these genes are known or suspected to be involved in immune system function. The most significant genetic risk factors for rheumatoid arthritis are variations in human leukocyte antigen (HLA) genes, especially the HLA-DRB1 gene. The proteins produced from HLA genes help the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). Changes in other genes appear to have a smaller impact on a person's overall risk of developing the condition.

Other, nongenetic factors are also believed to play a role in rheumatoid arthritis. These factors may trigger the condition in people who are at risk, although the mechanism is unclear. Potential triggers include changes in sex hormones (particularly in women), occupational exposure to certain kinds of dust or fibers, and viral or bacterial infections. Long-term smoking is a well-established risk factor for developing rheumatoid arthritis; it is also associated with more severe signs and symptoms in people who have the disease.

Related Gene(s)

Changes in these genes are associated with rheumatoid arthritis.

  • AFF3
  • ARID5B
  • BLK
  • C5
  • CCL21
  • CCR6
  • CD2
  • CD28
  • CD40
  • CD5
  • CD58
  • CTLA4
  • FCGR2A
  • FCGR2B
  • GATA3
  • HLA-B
  • HLA-DPB1
  • HLA-DRB1
  • IKZF3
  • IL2
  • IL21
  • IL2RA
  • IL2RB
  • IL6R
  • IL6ST
  • IRAK1
  • IRF5
  • IRF8
  • KIF5A
  • PADI4
  • PIP4K2C
  • POU3F1
  • PRDM1
  • PRKCQ
  • PTPN22
  • PTPRC
  • PXK
  • RASGRP1
  • RBPJ
  • RCAN1
  • REL
  • RUNX1
  • SPRED2
  • STAT4
  • TAGAP
  • TLE3
  • TNFAIP3
  • TNFRSF14
  • TRAF1
  • TRAF6
  • TYK2

How do people inherit rheumatoid arthritis?

The inheritance pattern of rheumatoid arthritis is unclear because many genetic and environmental factors appear to be involved. However, having a close relative with rheumatoid arthritis likely increases a person's risk of developing the condition.

Where can I find information about diagnosis or management of rheumatoid arthritis?

These resources address the diagnosis or management of rheumatoid arthritis and may include treatment providers.

  • American College of Rheumatology: 2010 Rheumatoid Arthritis Classification (http://www.rheumatology.org/practice/clinical/classification/ra/ra_2010.asp)
  • American College of Rheumatology: Clinical Practice Guidelines for Rheumatoid Arthritis (http://www.rheumatology.org/Practice/Clinical/Guidelines/Rheumatoid_Arthritis_%28Members__Only%29/)
  • Genetic Testing Registry: Rheumatoid arthritis (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0003873)

You might also find information on the diagnosis or management of rheumatoid arthritis in Educational resources (http://ghr.nlm.nih.gov/condition/rheumatoid-arthritis/show/Educational+resources) and Patient support (http://ghr.nlm.nih.gov/condition/rheumatoid-arthritis/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about rheumatoid arthritis?

You may find the following resources about rheumatoid arthritis helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for rheumatoid arthritis?

  • arthritis, rheumatoid
  • RA

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about rheumatoid arthritis?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding rheumatoid arthritis?

anemia ; arthritis ; autoimmune ; bacteria ; cartilage ; chronic ; disability ; fever ; gene ; HLA ; immune system ; inflammation ; inheritance ; inheritance pattern ; joint ; leukocyte ; population ; risk factors ; tissue

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

  • Carmona L, Cross M, Williams B, Lassere M, March L. Rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2010 Dec;24(6):733-45. doi: 10.1016/j.berh.2010.10.001. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21665122?dopt=Abstract)
  • Diogo D, Kurreeman F, Stahl EA, Liao KP, Gupta N, Greenberg JD, Rivas MA, Hickey B, Flannick J, Thomson B, Guiducci C, Ripke S, Adzhubey I, Barton A, Kremer JM, Alfredsson L; Consortium of Rheumatology Researchers of North America; Rheumatoid Arthritis Consortium International, Sunyaev S, Martin J, Zhernakova A, Bowes J, Eyre S, Siminovitch KA, Gregersen PK, Worthington J, Klareskog L, Padyukov L, Raychaudhuri S, Plenge RM. Rare, low-frequency, and common variants in the protein-coding sequence of biological candidate genes from GWASs contribute to risk of rheumatoid arthritis. Am J Hum Genet. 2013 Jan 10;92(1):15-27. doi: 10.1016/j.ajhg.2012.11.012. Epub 2012 Dec 20. (http://www.ncbi.nlm.nih.gov/pubmed/23261300?dopt=Abstract)
  • Eyre S, Bowes J, Diogo D, Lee A, Barton A, Martin P, Zhernakova A, Stahl E, Viatte S, McAllister K, Amos CI, Padyukov L, Toes RE, Huizinga TW, Wijmenga C, Trynka G, Franke L, Westra HJ, Alfredsson L, Hu X, Sandor C, de Bakker PI, Davila S, Khor CC, Heng KK, Andrews R, Edkins S, Hunt SE, Langford C, Symmons D; Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate; Wellcome Trust Case Control Consortium, Concannon P, Onengut-Gumuscu S, Rich SS, Deloukas P, Gonzalez-Gay MA, Rodriguez-Rodriguez L, Ärlsetig L, Martin J, Rantapää-Dahlqvist S, Plenge RM, Raychaudhuri S, Klareskog L, Gregersen PK, Worthington J. High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis. Nat Genet. 2012 Dec;44(12):1336-40. doi: 10.1038/ng.2462. Epub 2012 Nov 11. (http://www.ncbi.nlm.nih.gov/pubmed/23143596?dopt=Abstract)
  • Raychaudhuri S, Sandor C, Stahl EA, Freudenberg J, Lee HS, Jia X, Alfredsson L, Padyukov L, Klareskog L, Worthington J, Siminovitch KA, Bae SC, Plenge RM, Gregersen PK, de Bakker PI. Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis. Nat Genet. 2012 Jan 29;44(3):291-6. doi: 10.1038/ng.1076. (http://www.ncbi.nlm.nih.gov/pubmed/22286218?dopt=Abstract)
  • Stahl EA, Raychaudhuri S, Remmers EF, Xie G, Eyre S, Thomson BP, Li Y, Kurreeman FA, Zhernakova A, Hinks A, Guiducci C, Chen R, Alfredsson L, Amos CI, Ardlie KG; BIRAC Consortium, Barton A, Bowes J, Brouwer E, Burtt NP, Catanese JJ, Coblyn J, Coenen MJ, Costenbader KH, Criswell LA, Crusius JB, Cui J, de Bakker PI, De Jager PL, Ding B, Emery P, Flynn E, Harrison P, Hocking LJ, Huizinga TW, Kastner DL, Ke X, Lee AT, Liu X, Martin P, Morgan AW, Padyukov L, Posthumus MD, Radstake TR, Reid DM, Seielstad M, Seldin MF, Shadick NA, Steer S, Tak PP, Thomson W, van der Helm-van Mil AH, van der Horst-Bruinsma IE, van der Schoot CE, van Riel PL, Weinblatt ME, Wilson AG, Wolbink GJ, Wordsworth BP; YEAR Consortium, Wijmenga C, Karlson EW, Toes RE, de Vries N, Begovich AB, Worthington J, Siminovitch KA, Gregersen PK, Klareskog L, Plenge RM. Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. Nat Genet. 2010 Jun;42(6):508-14. doi: 10.1038/ng.582. Epub 2010 May 9. (http://www.ncbi.nlm.nih.gov/pubmed/20453842?dopt=Abstract)
  • Viatte S, Plant D, Raychaudhuri S. Genetics and epigenetics of rheumatoid arthritis. Nat Rev Rheumatol. 2013 Mar;9(3):141-53. doi: 10.1038/nrrheum.2012.237. Epub 2013 Feb 5. Review. (http://www.ncbi.nlm.nih.gov/pubmed/23381558?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: September 2013
Published: November 17, 2014