The subunit of IL-23 (IL12B) and its receptor (IL23R) gene single-nucleotide polymorphisms (SNPs) have been shown to be associated with several autoimmune diseases such as inflammatory bowel disease, psoriasis and ankylosing spondylitis.
In order to address the possibility that the MICA gene located 47 kb upstream from HLA-B is involved in the pathogenesis of ankylosing spondylitis (AS), we have investigated microsatellite polymorphism in the transmembrane region of MICA in Caucasian patients with AS.
ERAP1 variants associated with reduced endopeptidase activity appear to be protective against AS, raising the possibility that ERAP1 inhibition could represent a future treatment strategy.
This study demonstrates that natural ERAP1 polymorphism affects HLA-B27 antigen presentation and stability in vivo and proposes a mechanism for the interaction between these molecules in AS.
Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized with heterotopic ossification of the axis joints ligaments, resulting in joint disability.
This is first confirmation in a non-Caucasian population that genetic polymorphisms in ARTS1 are associated with AS, implicating common pathogenetic mechanisms in Korean and Caucasian patients with AS.
Results showed that the haplotype H4, containing ERAP1 SNPs associated with high enzymatic activity, together with the presence of ERAP2 expression, significantly increased the risk of AS (OR = 1.97, 95% CI = 1.21-3.21, p<sub>corr</sub> = 0.048).
Previously, we reported a triplet repeat polymorphism in the transmembrane region within the MICA gene closely linked to HLA-B in a limited number of B27-positive Caucasian patients with ankylosing spondylitis (AS) (N = 48).
Because of the location of the TNF gene in the vicinity of the HLA-B locus, and the prominent role in inflammation of its product, we investigated the association between AS and two G to A transition polymorphisms located at position -238 and -376 in the promoter region of the TNF gene.