PMID- 32360304 OWN - NLM STAT- MEDLINE DCOM- 20210708 LR - 20210708 IS - 1879-0542 (Electronic) IS - 0165-2478 (Linking) VI - 223 DP - 2020 Jul TI - Endoplasmic reticulum aminopeptidase 2 gene single nucleotide polymorphisms in association with susceptibility to ankylosing spondylitis in an Iranian population. PG - 97-105 LID - S0165-2478(20)30211-X [pii] LID - 10.1016/j.imlet.2020.04.015 [doi] AB - 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)-gamma, and tumor necrosis factor (TNF)-alpha 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. CI - Copyright (c) 2020 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved. FAU - Ebrazeh, Mehrdad AU - Ebrazeh M AD - Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran. FAU - Nojavan, Mohammad AU - Nojavan M AD - Department of Laboratory Medicine, Alfa Medical Laboratory, Urmia, Iran. FAU - Abdi-Shayan, Shiva AU - Abdi-Shayan S AD - Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. FAU - Salimifard, Sevda AU - Salimifard S AD - Department of Hematology and Blood Transfusion, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. FAU - Dolatshahi, Elahe AU - Dolatshahi E AD - Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran. FAU - Aslani, Saeed AU - Aslani S AD - Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. FAU - Hemmatzadeh, Maryam AU - Hemmatzadeh M AD - Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran. FAU - Babaie, Farhad AU - Babaie F AD - Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran. FAU - Ghanavatinejad, Alireza AU - Ghanavatinejad A AD - Department of Immunology, Pasteur Institute of Iran, Tehran, Iran. FAU - Azizi, Gholamreza AU - Azizi G AD - Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran. FAU - Jadidi-Niaragh, Farhad AU - Jadidi-Niaragh F AD - Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. FAU - Zamani, Neda AU - Zamani N AD - Department of Cell and Molecular Biology, Marand Branch, Islamic Azad University, Marand, Iran. FAU - Mohammadi, Hamed AU - Mohammadi H AD - Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran; Department of Immunology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran. Electronic address: h.mohammadi@abzums.ac.ir. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200429 PL - Netherlands TA - Immunol Lett JT - Immunology letters JID - 7910006 RN - 0 (HLA-B27 Antigen) RN - EC 3.4.11.- (Aminopeptidases) RN - EC 3.4.11.- (ERAP2 protein, human) SB - IM MH - Adult MH - Aminopeptidases/*genetics MH - Case-Control Studies MH - Female MH - Gene Frequency MH - Genetic Association Studies MH - Genetic Predisposition to Disease MH - *Genotype MH - HLA-B27 Antigen/genetics MH - Humans MH - Iran MH - Male MH - Middle Aged MH - Polymorphism, Single Nucleotide MH - Spondylitis, Ankylosing/*genetics OTO - NOTNLM OT - Ankylosing spondylitis OT - Endoplasmic reticulum aminopeptidase OT - Human leukocyte antigen-B27 OT - Inflammation OT - Single nucleotide polymorphisms COIS- Declaration of Competing Interest The authors declare that there is no conflict of interest to declare. EDAT- 2020/05/04 06:00 MHDA- 2021/07/09 06:00 CRDT- 2020/05/04 06:00 PHST- 2020/03/31 00:00 [received] PHST- 2020/04/25 00:00 [accepted] PHST- 2020/05/04 06:00 [pubmed] PHST- 2021/07/09 06:00 [medline] PHST- 2020/05/04 06:00 [entrez] AID - S0165-2478(20)30211-X [pii] AID - 10.1016/j.imlet.2020.04.015 [doi] PST - ppublish SO - Immunol Lett. 2020 Jul;223:97-105. doi: 10.1016/j.imlet.2020.04.015. Epub 2020 Apr 29.