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Association of the Genetic Variants in the Endoplasmic Reticulum Aminopeptidase 2 Gene With Ankylosing Spondylitis Susceptibility Publisher Pubmed



Ebrazeh M1 ; Ezzatifar F2, 3 ; Torkamandi S4 ; Mohammadi FS5 ; Salimifard S6 ; Gowhari Shabgah A7 ; Hemmatzadeh M8 ; Aslani S9 ; Babaie F10 ; Jadidiniaragh F11, 12 ; Gholizadeh Navashenaq J13 ; Mohammadi H14, 15
Authors
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Authors Affiliations
  1. 1. Department of Biology, Bonab Branch, Islamic Azad University, Bonab, Iran
  2. 2. Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
  3. 3. Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran
  4. 4. Faculty of Medicine, Department of Medical Genetics and Immunology, Urmia University of Medical Sciences, Urmia, Iran
  5. 5. Immunology Research Center, Inflammation and Inflammatory Diseases Division, Medical School, Mashhad University of Medical Sciences, Mashhad, Iran
  6. 6. Faculty of Medicine, Department of Hematology and Blood Transfusion, Mashhad University of Medical Sciences, Mashhad, Iran
  7. 7. School of Medicine, Bam University of Medical Sciences, Bam, Iran
  8. 8. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
  9. 9. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  10. 10. Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran
  11. 11. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  12. 12. Faculty of Medicine, Department of Immunology, Tabriz University of Medical Sciences, Tabriz, Iran
  13. 13. Noncommunicable Diseases Research Center, Bam University of Medical Sciences, Bam, Iran
  14. 14. Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
  15. 15. Department of Immunology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran

Source: International Journal of Rheumatic Diseases Published:2021


Abstract

Background: Genetic polymorphisms in the endoplasmic reticulum aminopeptidase gene ERAP2 has been attributed with the etiopathogenesis of ankylosing spondylitis (AS). Here we assessed the association of ERAP2 gene single nucleotide polymorphisms (SNPs) with AS predisposition in Iranian patients and determined their effect on the inflammatory state of the patients. Methods: For genotyping of rs2548538, rs2287988, and rs17408150 SNPs using a real-time allelic discrimination approach, DNA was extracted from the whole blood of 250 AS patients and 250 healthy individuals. RNA of the peripheral blood mononuclear cells was separated, cDNA was synthesized, and transcriptional levels of cytokines, including interleukin (IL)-17A, IL-23, IL-10, and transforming growth factor-β, were measured. Enzyme-linked immunosorbent assay was used to measure the serum concentration on the cytokines. Results: Three ERAP2 gene SNPs were not associated significantly with AS risk. Nonetheless, rs2287988 and rs17408150 SNPs showed statistically significant association with susceptibility to the disease in those AS patients who were positive for human leukocyte antigen (HLA)-B27. Transcriptional level and serum concentration of IL-17A and IL-23 were higher, but those of IL-10 were lower in both AS patients and the HLA-B27-positive patient group relative to the control group. Nevertheless, ERAP2 gene SNPs in the HLA-B27-positive AS patients did not affect the transcription level and serum concentration of cytokines. Conclusions: ERAP2 gene rs2287988 and rs17408150 SNPs are associated with susceptibility to AS, but they are probably not determining the levels of IL-17A, IL-23, and IL-10 in this disease. © 2021 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd
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