PMID- 33550689
OWN - NLM
STAT- MEDLINE
DCOM- 20211110
LR  - 20211110
IS  - 1756-185X (Electronic)
IS  - 1756-1841 (Linking)
VI  - 24
IP  - 4
DP  - 2021 Apr
TI  - Association of the genetic variants in the endoplasmic reticulum aminopeptidase 2 
      gene with ankylosing spondylitis susceptibility.
PG  - 567-581
LID - 10.1111/1756-185X.14079 [doi]
AB  - 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-beta, 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.
CI  - (c) 2021 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons 
      Australia, Ltd.
FAU - Ebrazeh, Mehrdad
AU  - Ebrazeh M
AD  - Department of Biology, Bonab Branch, Islamic Azad University, Bonab, Iran.
FAU - Ezzatifar, Fatemeh
AU  - Ezzatifar F
AD  - Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran 
      University of Medical Sciences, Sari, Iran.
AD  - Student Research Committee, Mazandaran University of Medical Sciences, Sari, 
      Iran.
FAU - Torkamandi, Shahram
AU  - Torkamandi S
AD  - Faculty of Medicine, Department of Medical Genetics and Immunology, Urmia 
      University of Medical Sciences, Urmia, Iran.
FAU - Mohammadi, Fatemeh Sadat
AU  - Mohammadi FS
AD  - Immunology Research Center, Inflammation and Inflammatory Diseases Division, 
      Medical School, Mashhad University of Medical Sciences, Mashhad, Iran.
FAU - Salimifard, Sevda
AU  - Salimifard S
AD  - Faculty of Medicine, Department of Hematology and Blood Transfusion, Mashhad 
      University of Medical Sciences, Mashhad, Iran.
FAU - Gowhari Shabgah, Arezoo
AU  - Gowhari Shabgah A
AD  - School of Medicine, Bam University of Medical Sciences, Bam, Iran.
FAU - Hemmatzadeh, Maryam
AU  - Hemmatzadeh M
AD  - Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
FAU - Aslani, Saeed
AU  - Aslani S
AD  - Department of Immunology, School of Medicine, Tehran University of Medical 
      Sciences, Tehran, Iran.
FAU - Babaie, Farhad
AU  - Babaie F
AD  - Cellular and Molecular Research Center, Urmia University of Medical Sciences, 
      Urmia, Iran.
FAU - Jadidi-Niaragh, Farhad
AU  - Jadidi-Niaragh F
AD  - Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
AD  - Faculty of Medicine, Department of Immunology, Tabriz University of Medical 
      Sciences, Tabriz, Iran.
FAU - Gholizadeh Navashenaq, Jamshid
AU  - Gholizadeh Navashenaq J
AD  - Noncommunicable Diseases Research Center, Bam University of Medical Sciences, 
      Bam, Iran.
FAU - Mohammadi, Hamed
AU  - Mohammadi H
AUID- ORCID: 0000-0002-0736-6211
AD  - Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, 
      Karaj, Iran.
AD  - Department of Immunology, School of Medicine, Alborz University of Medical 
      Sciences, Karaj, Iran.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
DEP - 20210207
PL  - England
TA  - Int J Rheum Dis
JT  - International journal of rheumatic diseases
JID - 101474930
RN  - 0 (Biomarkers)
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - EC 3.4.11.- (Aminopeptidases)
RN  - EC 3.4.11.- (ERAP2 protein, human)
SB  - IM
MH  - Adult
MH  - Aminopeptidases/*genetics
MH  - Biomarkers/blood
MH  - Case-Control Studies
MH  - Cytokines/blood/genetics
MH  - Female
MH  - Genetic Association Studies
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - Inflammation Mediators/blood
MH  - Iran
MH  - Male
MH  - Middle Aged
MH  - Phenotype
MH  - *Polymorphism, Single Nucleotide
MH  - Risk Assessment
MH  - Risk Factors
MH  - Spondylitis, Ankylosing/diagnosis/*genetics/immunology
OTO - NOTNLM
OT  - ankylosing spondylitis
OT  - endoplasmic reticulum aminopeptidase 2
OT  - human leukocyte antigen-B27
OT  - inflammation
OT  - single nucleotide polymorphisms
EDAT- 2021/02/08 06:00
MHDA- 2021/11/11 06:00
CRDT- 2021/02/07 20:54
PHST- 2021/01/10 00:00 [revised]
PHST- 2020/12/17 00:00 [received]
PHST- 2021/01/13 00:00 [accepted]
PHST- 2021/02/08 06:00 [pubmed]
PHST- 2021/11/11 06:00 [medline]
PHST- 2021/02/07 20:54 [entrez]
AID - 10.1111/1756-185X.14079 [doi]
PST - ppublish
SO  - Int J Rheum Dis. 2021 Apr;24(4):567-581. doi: 10.1111/1756-185X.14079. Epub 2021 
      Feb 7.