**14. Rheumatic diseases**

In considering the role of pathogenetic factors in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and ankylosing spondylitis (AS), special emphasis should be laid on risk genes and the extent to which they overlap.

According to GWA data, the contribution of MHC to RA risk can approximately be estimated as 30%, HLA-DRB1 alleles (e.g., DRB1\*0401 with OR of 3) being critical for RA. Additional loci essential for estimating RA risks were identified by high-density genotyping as HLA-DP in patients with anticyclic citrullinated peptide antibodies, (*HLA-DR2(DRB1\*1501))* and *DR3 (DRB1\*0301)* alleles in the MHC class II region with Ors of 2, risk variants in the MHC class III cluster encoding the TNF gene and the C2 complement components C4A and C4B.

Other loci in the MHC class III region associated with SLE include: the SKIV2L gene encoding the superkiller viralicidic activity of a 2-like protein, the PTPN22 gene, TNFAIP3 and TRAF1-C5 loci (TNF-associated signalling pathway genes), Integrin-α-M (ITGAM), STAT4, IL23R and a number of other genes.
