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).
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