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genetics of rheumatoid arthritis

Genetics: 1) susceptibility conferred by HLA-DR genes a) DR4 (Dw4, Dw14, Dw15), DR1, DR6, DR10 b) susceptibility is conferred by shared epitope on the beta chain of HLA-DR molecule c) dysregulation of T-cell selection & maturation d) genetic variation in HAVCR2 may influence susceptibility e) susceptibility linked to FCRL3 2) mutations in the promoter region of NFKBIL1 represent the second rheumatoid arthritis susceptibility locus within the HLA region 3) studies of concordance suggest involvement of other genes a) RANK 18q21, regulates osteoclast differentiation b) 1q43 (unknown genes), linkage with SLE c) 6q21 (unknown), 1p13 (unknown) d) gene for SCL22A4 - regulates lymphocyte activation - contributes to local inflammation e) RUNX1, regulates expression of SCL122A4 f) gene for corticotrophin releasing hormone - defective hypothalamic-pituitary axis response to inflammation g) CC chemokine peptides are found in high levels in synovial fluid from patients with RA - CCCCL15(22-92), CCL15(25-92) & CCL15(29-92) - CCL23(19-99), CCL23(22-99), CCL23(27-99), CCL23(30-99) h) other implicated genes IL22RA1, MICB, CD97, SLC22A4, CD157, PTPN22

General

genetics rheumatology

Database Correlations

OMIM 180300

References

  1. Turesson C, Matteson EL. Genetics of rheumatoid arthritis. Mayo Clin Proc. 2006 Jan;81(1):94-101. Review. PMID: 16438485