title: Non-major histocompatibility complex rheumatoid arthritis susceptibility genes.
abstract: Recent results from genetic and treatment studies have shed new light on chronic inflammatory and autoimmune diseases such as rheumatoid arthritis (RA). In particular, genome-wide association studies (GWAS) have provided supportive evidence that RA is a disease with a strong genetic background. Interestingly, a series of candidate genes have been identified outside of the classical major histocompatibility (MHC) locus, which had long been regarded as the major contributor to the pathogenesis of this disease. Among these genes, PTPN22 plays an outstanding role. CD40, STAT4, PRM1, and TNFAIP3 also seem to be of relevance. Interestingly, there is a significant overlap between RA susceptibility genes and those of other autoimmune diseases such as systemic lupus erythematosus (SLE) and type 1 diabetes, which suggests common pathogenic mechanisms. Genetic analyses may not only provide new insights into the pathogenesis of RA, but may also open new avenues for therapeutic approaches, because overactive immune-signaling pathways might specifically be addressed by biologic therapies. However, the predictive value of many of the recent findings of large-scale genetic analyses in identifying new genetic polymorphisms remains low. We describe the current knowledge about the role of non-MHC genes in the pathogenesis of rheumatoid arthritis.
authors.affiliation: Department of Dermatology, Venereology and Allergology, University of Leipzig, Leipzig, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Kunz
authors.forename: Saleh M
authors.initials: SM
authors.lastname: Ibrahim
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics*; D019013:CD40 Antigens / Q000235:genetics; D004268:DNA-Binding Proteins; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D055106:Genome-Wide Association Study; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011479:Protamines / Q000235:genetics; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D050797:STAT4 Transcription Factor / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
chemical_list: D019013:CD40 Antigens; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; C082073:PRM1 protein, human; D011479:Protamines; D050797:STAT4 Transcription Factor; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3