In this study, we aimed to determine the association of ERAP1 gene SNPs (rs30187 and rs2287987) with AS risk as well as their effect on the mRNA expression of pro-inflammatory and anti-inflammatory cytokines, with emphasis on the immunoregulation of the IL-17/IL-23 pathway, in an Iranian population.
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).
Based on our recent findings, in this perspective article we speculate that the <i>E</i>ndoplasmic <i>R</i>eticulum <i>A</i>mino <i>P</i>eptidases, ERAP1 and 2, associated with AS and involved in antigen presentation, underwent co-selection by malaria.
Genome-wide association study in Turkish and Iranian populations identify rare familial Mediterranean fever gene (MEFV) polymorphisms associated with ankylosing spondylitis.
Our results provided a detailed spectrum of all the reported non-MHC AS susceptibility loci in Han Chinese, which comprehensively exhibited the ethnic heterogeneity of AS susceptibility and highlighted that 2p15, ERAP1 and NPEPPS-TBKBP1 region may play a critical role in AS pathogenesis across diverse populations.
Genetic variants of ERAP1 (leading to distinct allotypes) are linked with specific autoinflammatory disorders, such as ankylosing spondylitis and Behçet's disease.
Here, we intended to investigate the possible association of ERAP1 gene single nucleotide polymorphisms (SNPs) with AS susceptibility in Iranian patients.
Together, our data suggests that ERAP1<sup>-/-</sup> mice may serve as a useful animal model for studying pathogenesis of intestinal, skeletal, and immunological manifestations of Ankylosing Spondylitis.
In accordance with studies demonstrating that polymorphisms that increase aminopeptidase activity predispose to immune disease, the increased risk also attributed to increased expression of ERAP1 and ERAP2 supports the notion of using aminopeptidase inhibition to treat AS and other ERAP-associated conditions.
However, there was a significant association between ERAP1 polymorphisms rs30187 and rs27037 (T vs C, OR, 1.322, 95% CI = 1.240-10410, P <.05; T vs G, OR, 1.247, 95% CI = 1.149-1.353; P <.05; respectively) and AS susceptibility.
To explore the association between five polymorphisms in endoplasmic reticulum associated aminopeptidase 1 (ERAP1) gene and risk of ankylosing spondylitis (AS) in a Chinese population.
Ranking the Contribution of Ankylosing Spondylitis-associated Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) Polymorphisms to Shaping the HLA-B*27 Peptidome.
In this review, several points are discussed and summarized including recent advances on the role of the IL-17/IL-23 immune pathway in the pathogenesis of AS, HLA-B27, and ERAP 1 and 2 mediated pathogenesis, AS-related microbiota compositions, and new potential therapies for AS.
Segregating according to HLAB27 status did not alter the lack of association. rs30187 SNP in ERAP1 does not confer risk of developing ERA or AS in the Asian Indian population.
In conclusion, the results of the two-stage bioinformatics analysis supported the hypothesis that ERAP1 may present an important susceptibility gene for AS.
Deletion of Erap1 was permissive for the AS-like phenotype, increased mean peptide length and increased the frequency of C-terminal hydrophobic residues and of N-terminal Ala, Ser, or Lys.
GWAS have also shown the potential associations between ERAP single nucleotide polymorphisms (SNP) loci and susceptibility to several autoimmune diseases, and ERAP1 and ERAP2 polymorphisms are related to HLA class I-associated diseases, including ankylosing spondylitis and Behçet's disease.
Functional studies in humans have extended knowledge of established genetic risk factors for ankylosing spondylitis that include ERAP1, ERAP2, and interleukin-23R.