Rheumatoid arthritis genetic factors

Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown aetiology with some autoimmune features. Current thinking favours the hypothesis that interplay between genetic factors, sex hormones, and possibly an infectious agent or another immune activating agent initiates an autoimmune pathogenic mechanism that culminates in a disease with inflammatory and destructive features. 

Corominas, H., Domenech, M., Laiz, A., et al. (2003) Is thiopuiine methyltransferase genetic polymorphism a major factor for withdrawal of azathioprine in rheumatoid arthritis patients Rheumatology. 42, 40-45. 

Mulcahy, B., Waldron-Lynch, F., McDermott, M. F., et al. (1996) Genetic variability in the tumor necrosis factor-lymphotoxin region influences susceptibility to rheumatoid arthritis. American Journal of Human Genetics. 59, 676-683. 

The cause of rheumatoid arthritis is unknown, but it is thought that a mixture of genetic and environmental factors affect whether someone develops the condition. Some of the factors that have been linked to the development of rheumatoid arthritis include ... 

Rheumatoid arthritis is a chronic, inflammatory, autoimmune disease of unknown etiology that if left untreated results in progressive joint destruction, deformity, disability, and premature death. Theories of possible etiologies include genetic, hormonal, viral, autoimmune, and environmental factors. The disease peaks between the fourth through sixth decades of life and is two to three times more common in women than in men. Differences in prevalence rates between ethnic groups are small. 

Maxwell JR, Potter C, Hyrich KL, Barton A, Worthington J, Isaacs JD et al (2008) Association of the tumour necrosis factor-308 variant with differential response to anti-TNF agents in the treatment of rheumatoid arthritis. Hum Mol Genet 17 3532-3538... 

Padyukov L, Lampa J, Heimburger M, Ernestam S, Cederholm T, Lundkvist I et al (2003) Genetic markers for the efficacy of tumour necrosis factor blocking therapy in rheumatoid arthritis. Ann Rheum Dis 62 526-529... 

Plant D, Bowes J, Potter C, Hyrich KL, Morgan AW, Wilson AG et al (2011) Genome-wide association study of genetic predictors of anti-tumor necrosis factor treatment efficacy in rheumatoid arthritis identifies associations with polymorphisms at seven loci. Arthritis Rheum 63 645-653... 

Rheumatoid arthritis (RA) In most Caucasian populations, susceptibility to (or severity of) RA is due to a closely related set of polymorphic sequences (the shared epitope ) on several different HLA-DRB1 alleles, especially certain subtypes of the DR4 and DR1 allelic families (Gregersen et al., 1987 Nepom, 1998). Some genetically distant populations exhibit a different association (e.g. HLA-DR9 in Native Americans, HLA-DR3 in RA patients from Finland) (Hakala et al., 1997). Ferucci et al. (2005) found genetic susceptibility to the development of RA in the American Indian/Alaskan Native populations at least partially associated with different HLA alleles, such as HLA-DRB1 1402, among other possible genetic factors yet elucidated. 

Ferucci et al. (2005) described a relationship of genetic factors and prevalence of rheumatoid arthritis and presented evidence for the increased prevalence of a severe, early-onset rheumatoid arthritis in some populations of American Indians (including Alaskan Natives) that is associated with a high frequency of some HLA alleles, such as HLA-DRB 1 1402. However, evidence suggests that other genetic factors or components, possibly non-HLA-associated genes, play contributing roles in rheumatoid arthritis risk. 

Martinez A, Fernandez-Arquero M, Pascual-Salcedo D, Conejero L, Alves H, Balsa A, de la Concha EG (2000) Primary association of tumor necrosis factor-region genetic markers with susceptibility to rheumatoid arthritis. Arthritis Rheum, 43 1366-1370. 

E. Abnormal Immune Responses Abnormal immune responses include hypersensitivity, autoimmunity, and inununodeficiency states. Immediate hypersensitivity is usually antibody-mediated and includes anaphylaxis and hemolytic disease of the newborn delayed hyptersensitiv-ity, associated with extensive tissue damage, is cell-mediated. Autoinununity arises from self-reactive lymphocytes that react to one s own molecules, or self-antigens. Examples of autoimmune diseases that are amenable to dmg treatment include rheumatoid arthritis and systemic lupus erythematosus. Immunodeficiency states may be genetically acquired (eg, Di George s syndrome) or result from extrinsic factors (eg, AIDS). 

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