Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes severe joint pain and eventually joint deformity. Recent large cohort studies and the rapid progression of genotyping platforms have enabled identification of more than 30 susceptibility genes for RA. HLA is the major genetic determinant for RA for which a shared epitope hypothesis (70th-74th amino acids of HLA-DRβ chain determine susceptibility) has been accepted. However, recent detailed single nucleotide polymorphism (SNP) typing of the HLA region and imputation method revealed that the most important amino acid positions of the HLA-DRβ chain are the 11th in addition to the 71st and the 74th. HLA-B (at position 9) and HLA-DPB1 (at position 9) are also important determinants. This revised shared epitope hypothesis will form a new theory for HLA association. Another topic is that anti-citrullinated protein antibody (ACPA)-negative RA has been shown to be genetically different from ACPA-positive RA. Many susceptibility genes including HLA were not associated with ACPA-negative RA; however, we have shown that some HLA alleles are associated with ACPA-negative RA. In this review, we present some new findings regarding HLA as well as some recently discovered susceptibility genes for RA.
