Copy number variation of IL17RA gene and its association with the ankylosing spondylitis risk in Iranian patients: a case-control study.

Background: 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.

Methods: 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).

Results: 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.

Conclusions: 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.