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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 additional SNPs in the MHC region are rs4678 and rs2442728; these appear to be independent of HLA-DRB1.[PMID 19116923]
- A study [PMID 20498205] of 3,000 RA patients from 6 European countries and an accompanying meta-analysis confirmed 18 non-HLA SNPs as associated with RA risk, primarily:
- Two SNPs from a ~2,000+ patient study [PMID 17804836]:
- 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:
- The 11 SNPs reported in a recent (2007) large study [PMID 17554300]:
- rs7528684, a SNP in the promoter of the FCRL3 gene, observed in both Japanese and Caucasian populations [PMID 17179172]
- rs2476601, a SNP in the PTPN22 gene, also associated with numerous other autoimmune disorders [PMID 17135225]
- [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