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Endoplasmic Reticulum Aminopeptidase 2 Gene Single Nucleotide Polymorphisms in Association With Susceptibility to Ankylosing Spondylitis in an Iranian Population Publisher Pubmed



Ebrazeh M1 ; Nojavan M2 ; Abdishayan S3 ; Salimifard S4 ; Dolatshahi E1 ; Aslani S5 ; Hemmatzadeh M6 ; Babaie F7 ; Ghanavatinejad A8 ; Azizi G1 ; Jadidiniaragh F3, 9 ; Zamani N10 ; Mohammadi H1, 11
Authors
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Authors Affiliations
  1. 1. Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
  2. 2. Department of Laboratory Medicine, Alfa Medical Laboratory, Urmia, Iran
  3. 3. Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
  4. 4. Department of Hematology and Blood Transfusion, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
  5. 5. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
  7. 7. Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran
  8. 8. Department of Immunology, Pasteur Institute of Iran, Tehran, Iran
  9. 9. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  10. 10. Department of Cell and Molecular Biology, Marand Branch, Islamic Azad University, Marand, Iran
  11. 11. Department of Immunology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran

Source: Immunology Letters Published:2020


Abstract

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. © 2020 European Federation of Immunological Societies
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