Ankylosing spondylitis (AS) is considered as a subtype of spondyloarthritis (SpA) that mainly leads to fatigue, stiffness, spinal ankylosis, and impaired physical functions with reduced quality of life. Interleukin (IL)-17A provokes additional inflammatory mediators and recruits immune cells to the inflamed site. IL17 expression increased in various inflammatory disorders including psoriasis, rheumatoid arthritis, multiple sclerosis, crohn’s disease, and ankylosing spondylitis. The current study aimed to evaluate the association of IL17RA copy number changes with the susceptibility to AS and their correlation to IL17RA expression in Iranian population. IL17RA copy number genotyping assessments were carried out in 455 AS patients and 450 healthy controls, using custom TaqMan CNV assays. TaqMan primers and probe were located in Chr.22:17109553 based on pre-designed IL17RA Copy Number Assay ID, Hs02339506_cn. mRNA expression of IL17RA was also measured by SYBR Green real-time polymerase chain reaction (PCR). A IL17RA copy number loss (< 2) was associated with AS compared to 2 copies as reference (OR:2.18, 95% CI: (1.38–3.44), P-value < 0.001) and increased the risk of AS. IL17RA mRNA expression showed a significant increase in peripheral blood mononuclear cells (PBMCs) of all AS individuals than controls. The mRNA expression level of 2 copies was significantly higher in AS patients. Our findings revealed that a low copy number of IL17RA might confer a susceptibility risk to AS. However, it is probably not directly involved in the regulation of IL17RA mRNA expression. Epigenetic mechanisms like DNA methylation, post-transcriptional, and -translational modifications that regulate the expression of the genes may contribute in upregulation of IL17RA mRNA expression in the loss of gene copy number condition.

中文翻译：

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伊朗患者IL17RA基因的拷贝数变异及其与强直性脊柱炎风险的关系。

强直性脊柱炎（AS）被认为是脊椎关节炎（SpA）的一种亚型，主要导致疲劳，僵硬，脊柱强直和身体功能受损，并降低生活质量。白介素（IL）-17A引起其他炎症介质，并将免疫细胞募集到发炎的部位。IL17表达在各种炎症性疾病中有所增加，包括牛皮癣，类风湿性关节炎，多发性硬化症，克罗恩氏病和强直性脊柱炎。本研究旨在评估IL17RA拷贝数变化与AS易感性及其与伊朗人群IL17RA表达的相关性。使用定制的TaqMan CNV分析在455名AS患者和450名健康对照中进行了IL17RA拷贝数基因分型评估。TaqMan引物和探针位于Chr.22中：基于预先设计的IL17RA拷贝数测定ID Hs02339506_cn的17109553。还通过SYBR Green实时聚合酶链反应（PCR）测量IL17RA的mRNA表达。IL17RA拷贝数丢失（<2）与AS相关，而2拷贝作为参考（OR：2.18，95％CI：（1.38–3.44），P值<0.001），增加了AS的风险。IL17RA mRNA表达显示所有AS个体的外周血单个核细胞（PBMC）均比对照组明显增加。AS患者中2个拷贝的mRNA表达水平显着更高。我们的发现表明，低拷贝数的IL17RA可能会给AS带来易感性风险。但是，它可能不直接参与IL17RA mRNA表达的调节。表观遗传机制，例如DNA甲基化，转录后，