Susceptibility to ERAP1 gene single nucleotide polymorphism modulates the inflammatory cytokine setting in ankylosing spondylitis
Maryam Hemmatzadeh
Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
Search for more papers by this authorFarhad Babaie
Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran
Search for more papers by this authorFatemeh Ezzatifar
Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran
Search for more papers by this authorFatemeh S. Mohammadi
Immunology Research Center, Inflammation and Inflammatory Diseases Division, Medical School, Mashhad University of Medical Sciences, Mashhad, Iran
Search for more papers by this authorMehrdad Ebrazeh
Department of Biology, Bonab Branch, Islamic Azad University, Bonab, Iran
Search for more papers by this authorShirin Golabi Aghdam
Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
Search for more papers by this authorMehrzad Hajaliloo
Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Search for more papers by this authorGholamreza Azizi
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
Search for more papers by this authorArezoo Gowhari Shabgah
Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Search for more papers by this authorNajibeh Shekari
Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
Search for more papers by this authorNasrin Sehati
Department of Genetic, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
Search for more papers by this authorRamin Hosseinzadeh
Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
Search for more papers by this authorCorresponding Author
Hamed Mohammadi
Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
Correspondence
Zohreh Babaloo and Hamed Mohammadi, Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Email: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Zohreh Babaloo
Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
Correspondence
Zohreh Babaloo and Hamed Mohammadi, Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Email: [email protected]; [email protected]
Search for more papers by this authorMaryam Hemmatzadeh
Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
Search for more papers by this authorFarhad Babaie
Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran
Search for more papers by this authorFatemeh Ezzatifar
Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran
Search for more papers by this authorFatemeh S. Mohammadi
Immunology Research Center, Inflammation and Inflammatory Diseases Division, Medical School, Mashhad University of Medical Sciences, Mashhad, Iran
Search for more papers by this authorMehrdad Ebrazeh
Department of Biology, Bonab Branch, Islamic Azad University, Bonab, Iran
Search for more papers by this authorShirin Golabi Aghdam
Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
Search for more papers by this authorMehrzad Hajaliloo
Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Search for more papers by this authorGholamreza Azizi
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
Search for more papers by this authorArezoo Gowhari Shabgah
Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Search for more papers by this authorNajibeh Shekari
Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
Search for more papers by this authorNasrin Sehati
Department of Genetic, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
Search for more papers by this authorRamin Hosseinzadeh
Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
Search for more papers by this authorCorresponding Author
Hamed Mohammadi
Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
Correspondence
Zohreh Babaloo and Hamed Mohammadi, Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Email: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Zohreh Babaloo
Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
Correspondence
Zohreh Babaloo and Hamed Mohammadi, Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Email: [email protected]; [email protected]
Search for more papers by this authorAbstract
Aim
To evaluate the association of ERAP1 gene single nucleotide polymorphisms (SNPs) with the risk of ankylosing spondylitis (AS) and their role in modulation of the inflammatory interleukin (IL)-17/IL-23 axis in the disease.
Methods
For genotyping, 190 AS cases and 190 healthy controls were enrolled. After DNA extraction, all the subjects were genotyped for rs17482078, rs469876, and rs27038 polymorphisms using single specific primer polymerase chain reaction (PCR) assay. After isolation of peripheral blood mononuclear cells, RNA extraction and complementary DNA synthesis, real-time PCR using SYBR Green master mix was employed to determine messenger RNA (mRNA) expression of IL-17A and IL-23 in PBMCs. Using enzyme-linked immunosorbent assay, the concentration of these cytokines was determined in serum samples.
Results
It was observed that the A allele of rs27038 polymorphism significantly increased AS risk (odds ratio [OR] = 1.53, 95% CI =1.11-2.12; P = 0.0096). Moreover, AA and AG genotypes of this SNP were associated with increased (OR = 2.89, 95% CI = 1.42-5.85; P = 0.0031) and decreased (OR = 0.57, 95% CI = 0.36-0.92; P = 0.021), respectively, risk of the disease. The rs27038 SNP was associated with C-reactive protein level. There were significantly increased mRNA and serum concentrations of both IL-17A and IL-23 in AS patients compared with controls. Furthermore, AS patients with the AA in comparison to other genotypes for rs27038 SNP indicated significantly increased mRNA and serum concentration levels for both cytokines.
Conclusions
This study demonstrated the association of ERAP1 gene rs27038 polymorphism with the risk of AS in an Iranian population. Additionally, it seems that rs27038 is involved in the modulation of the inflammatory IL-17/IL-23 axis in AS.
CONFLICT OF INTERESTS
None.
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