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Rheumatoid Arthritis

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Rheumatoid arthritis (RA) is a chronic autoimmune disorder typically involving most joints. For a general discussion, see Wikipedia.

Some SNPs may genetically predispose individuals to rheumatoid arthritis, and others may influence response to drugs, such as anti-inflammatories or analgesics, used in the treatment of RA.

Note that several cited papers study a particular form of RA, namely the subgroup of patients with severe rheumatoid arthritis who are characterized by the presence of autoantibodies against cyclic citrullinated peptide (anti-CCP-positive).

As of late 2013, the most comprehensive model predicting risk for rheumatoid arthritis, taking into account all 46 known RA-associated genetic loci, has at best "modest" success, and it was deemed by it's creators as deemed "insufficiently accurate for general population screening".[PMID 24092415] Just after that, in early 2014 another 42 RA-associated SNPs were published based on a meta-analysis of 30,000 RA patients, apparently bringing the total number to 101. However, no modeling was performed so it's unknown if these additional SNPs have brought screening any closer or even made overall RA risk estimates more accurate.10.1038/nature12873

Individual SNPs that have been reported to increase risk for RA include:

  • Many SNPs in the major histocompatibility complex (MHC) region, most often those tagging the shared epitope (SE) alleles of HLA-DRB1. The risk posed by MHC alleles is the largest of any single region or gene, accounting for ~30% of the heritable risk.
  • Two SNPs from a ~2,000+ patient study [PMID 17804836]:
    • rs2476601, a SNP in the PTPN22 gene
    • rs3761847, a SNP located in a region containing two genes relevant to chronic inflammation: TRAF1 (tumor necrosis factor receptor–associated factor 1), and C5 (complement component 5).
  • From looking just at 40 SNPs in the C5-TRAF1 region in 2,000 patients, a haplotype block of ~65Kb was identified that showed maximal association for one SNP 10.1371/journal.pmed.0040278:
    • rs10818488, a SNP in between the two genes
    • rs1953126, independently identified from this same region
  • A SNP upstream of the NOS3 gene, apparently lacking an entry in dbSNP [PMID 17009241]
  • [PMID 17216583] The functional haplotype of peptidylarginine deiminase IV (S55G, A82V and A112G) associated with susceptibility to rheumatoid arthritis dominates apoptosis of acute T leukemia Jurkat cells.

[PMID 17661906] The PTPN22 promoter polymorphism -1123G>C association cannot be distinguished from the 1858C>T association

interesting blog post relating RA to genetics, diet, and infection