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Review
. 2022 Jan;44(1):47-62.
doi: 10.1007/s00281-022-00912-0. Epub 2022 Jan 27.

Genetics of rheumatoid arthritis

Leonid Padyukov  1
Affiliations
Review

Genetics of rheumatoid arthritis

Leonid Padyukov. Semin Immunopathol. 2022 Jan.

Abstract

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease involving symmetric joints and is generally characterized by persistent pain, tenderness, and destruction of joints. The vast majority of RA patients produce autoantibodies, and immune cell involvement in disease development is well recognized, as is the contribution of other types of cells in synovial tissue, like fibroblasts. It is known that there are major genetic associations with the HLA locus, while multiple non-HLA genetic variants display relatively low risk of RA. Both HLA and non-HLA associations suggest that the profiles of genetic associations for autoantibody-positive vs. autoantibody-negative RA are different. Several alleles of HLA-DRB1 are associated with high risk for autoantibody-positive RA, with the strongest risk characterized by valine at position 11 of the protein sequence (HLA-DRB1*04 and *10 alleles). There is a strong protective effect for the risk of autoantibody-positive RA associated with HLA-DRB1*13 alleles. Although major genetic associations have been known for several years, understanding of the specific mechanisms in the development of increased risk of RA for these variations is work in progress. Current studies focus on the binding of immune receptors involved in recognition of putative peptides in activation of T cells, as well as investigation of cell signaling mechanisms. At least a part of RA risk could be explained by gene-gene and gene-environment interactions. There are currently more than 150 candidate loci with polymorphisms that associate with RA, mainly related to seropositive disease, and new discoveries are anticipated in the future from investigation of diverse human populations. This new research will help create a strong foundation for the continuing process of integrating genetic, epigenetic, transcriptomic, and proteomic data in studies of RA.

Keywords: Autoantibody; Autoimmunity; Genetic polymorphism; HLA; Inflammation; Rheumatoid arthritis.

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Conflict of interest statement

The author declares no competing interests.

Figures

Fig. 1
Fig. 1
Physical position of SNPs in association with rheumatoid arthritis in human chromosomes
Fig. 2
Fig. 2
PPI networks for the genes associated with rheumatoid arthritis
Fig. 3
Fig. 3
Hypothetical cell pathways based on PPI networks for some of the genes associated with rheumatoid arthritis
See this image and copyright information in PMC

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