BACKGROUND Ankylosing spondylitis (AS) is a chronic autoimmune disease, in which genetic polymorphisms are critically important in establishing inflammatory state. Endoplasmic reticulum aminopeptidase (ERAP) 2 gene has been implied to be involved in AS etiopathogenesis. The current study evaluated the association of ERAP2 gene single nucleotide polymorphisms (SNPs) with susceptibility to AS in an Iranian population. METHODS Two hundred and forty AS patients and 240 healthy individuals were recruited. DNA extraction was performed from whole blood samples and RNA content was isolated from peripheral blood mononuclear cells (PBMCs). Real-time allelic discrimination approach was exerted to genotype all subjects for rs2910686, rs2248374, and rs2549782 SNPs. After cDNA synthesis, mRNA expression of cytokines was determined. Enzyme-linked immunosorbent assay (ELISA) was exerted to evaluate the cytokine levels in serum of participants. RESULTS None of the SNPs were associated with AS risk in the whole population. However, allele and heterozygote genotype of rs2910686 SNP were associated significantly with higher risk of AS in Human leukocyte antigen (HLA)-B27 positive group. mRNA expression and serum concentrations of interleukin (IL)-17A, IL-23, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α was increased in AS patients compared with controls. Nonetheless, mRNA expression and serum levels of cytokines was not significantly different among HLA-B27 positive AS patients with different three genotypes for rs2910686 SNP. CONCLUSIONS AlthoughERAP2 gene rs2910686 polymorphism was significantly associated with increased risk of AS susceptibility, it might not be involved in regulation of the inflammatory cytokines during AS pathogenesis.

中文翻译：

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内质网氨基肽酶2基因单核苷酸多态性与易感性强直性脊柱炎在伊朗人口中有关。

背景强直性脊柱炎（AS）是一种慢性自身免疫性疾病，其中遗传多态性对于建立炎症状态至关重要。内质网氨肽酶（ERAP）2基因被暗示与AS的发病机制有关。目前的研究评估了ERAP2基因单核苷酸多态性（SNP）与伊朗人群中AS易感性的关系。方法招募240例AS患者和240例健康个体。从全血样品中提取DNA，并从外周血单个核细胞（PBMC）中分离RNA含量。应用实时等位基因鉴别方法对rs2910686，rs2248374和rs2549782 SNP的所有受试者进行基因分型。cDNA合成后，确定细胞因子的mRNA表达。进行了酶联免疫吸附试验（ELISA）以评估参与者血清中的细胞因子水平。结果在所有人群中，没有一个SNP与AS风险相关。但是，rs2910686 SNP的等位基因和杂合子基因型与人类白细胞抗原（HLA）-B27阳性组的AS较高风险显着相关。与对照组相比，AS患者的白细胞介素（IL）-17A，IL-23，干扰素（IFN）-γ和肿瘤坏死因子（TNF）-α的mRNA表达和血清浓度增加。尽管如此，在具有针对rs2910686 SNP的三种基因型的不同HLA-B27阳性AS患者中，mRNA表达和血清细胞因子水平没有显着差异。结论尽管ERAP2基因rs2910686多态性与AS易感性风险增加显着相关，