BACKGROUND Ankylosing spondylitis (AS) is a prototype of chronic inflammatory arthritis termed seronegative spondyloarthropathies that typically affects the joints. Among the non-Human leukocyte antigen (HLA) loci, the strongest association has been observed with Endoplasmic reticulum aminopeptidase 1 (ERAP1) gene single nucleotide polymorphisms (SNPs). Moreover, the effect of ERAP1 gene SNPs on the pro-inflammatory and anti-inflammatory cytokines in AS disease has still been poorly elucidated. 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. METHODS We performed Single specific primer (SSP)-PCR for genotyping of 160 AS patients and 160 healthy controls. After isolation of peripheral blood mononuclear cells (PBMCs), total RNA of PBMCs was isolated, complementary DNA (cDNA) was synthesized, and quantitative analyses of mRNA expression of cytokines were performed by Real-time PCR for 40 HLA-B27 positive AS patients and 40 healthy individuals as controls. RESULTS It was seen that T allele of rs30187 (OR = 1.54, 95% CI = 1.07-2.22, P =  0.017) and C allele of rs2287987 (OR 1.50, 95% CI 1.05-2.14, P = 0.024) were associated with the risk of AS. Both of these alleles were associated more strongly in the HLA-B27 positive AS patients. There was a significant overexpression of mRNAs of pro-inflammatory (IL-17A, IL-17F, IL-23, TNF-α and IFN-γ), while downregulation of anti-inflammatory cytokines (IL-10 and TGF-β) in PBMCs from 40 HLA-B27 positive AS patients in comparison to controls. AS patients with rs30187 SNP TT genotype expressed mRNA of IL-17A, IL-17F, and IL-23 significantly higher than patents with CT and CC genotypes for this SNP. CONCLUSIONS This study represented the association of ERAP1 gene rs30187 and rs2287987 polymorphism with the risk of AS. Additionally, it appears that rs30187 polymorphism may be involved in the immunomodulation of the IL-17/IL-23 pathway in the AS disease.

中文翻译：

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在强直性脊柱炎的促炎和抗炎细胞因子谱的免疫调节中评估ERAP1基因单核苷酸多态性。

背景技术强直性脊柱炎（AS）是一种慢性炎症性关节炎的原型，被称为典型地影响关节的血清阴性的脊椎关节病。在非人类白细胞抗原（HLA）基因座中，已观察到与内质网氨基肽酶1（ERAP1）基因单核苷酸多态性（SNP）的最强关联。而且，仍未充分阐明ERAP1基因SNP对AS疾病中促炎和抗炎细胞因子的作用。在这项研究中，我们旨在确定ERAP1基因SNPs（rs30187和rs2287987）与AS风险的关系，以及它们对促炎和抗炎细胞因子mRNA表达的影响，并着重于IL-1的免疫调节。 17 / IL-23途径，在伊朗人口中。方法我们对160例AS患者和160例健康对照进行了单特异性引物（SSP）-PCR。分离外周血单核细胞（PBMC）后，分离出PBMC的总RNA，合成互补DNA（cDNA），并通过实时PCR对40例HLA-B27阳性AS患者和40名健康个体作为对照。结果发现rs30187的T等位基因（OR = 1.54，95％CI = 1.07-2.22，P = 0.017）和rs2287987的C等位基因（OR 1.50，95％CI 1.05-2.14，P = 0.024）与AS的风险。这两个等位基因在HLA-B27阳性AS患者中相关性更强。促炎性基因（IL-17A，IL-17F，IL-23，TNF-α和IFN-γ）的mRNA明显过表达，与对照组相比，来自40例HLA-B27阳性AS患者的PBMC中的抗炎细胞因子（IL-10和TGF-β）下调。rs30187 SNP TT基因型的AS患者表达的IL-17A，IL-17F和IL-23的mRNA显着高于该SNP的CT和CC基因型的专利。结论本研究代表了ERAP1基因rs30187和rs2287987多态性与AS风险的关系。另外，看来rs30187多态性可能与AS疾病中IL-17 / IL-23途径的免疫调节有关。结论本研究代表了ERAP1基因rs30187和rs2287987多态性与AS风险的关系。另外，看来rs30187多态性可能与AS疾病中IL-17 / IL-23途径的免疫调节有关。结论本研究代表了ERAP1基因rs30187和rs2287987多态性与AS风险的关系。另外，看来rs30187多态性可能与AS疾病中IL-17 / IL-23途径的免疫调节有关。