Susceptibility to ERAP1 gene single nucleotide polymorphism modulates the inflammatory cytokine setting in ankylosing spondylitis.

Autor: Hemmatzadeh M; 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., Babaie F; Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran., Ezzatifar F; 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., Mohammadi FS; Immunology Research Center, Inflammation and Inflammatory Diseases Division, Medical School, Mashhad University of Medical Sciences, Mashhad, Iran., Ebrazeh M; Department of Biology, Bonab Branch, Islamic Azad University, Bonab, Iran., Golabi Aghdam S; Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran., Hajaliloo M; Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Azizi G; 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., Gowhari Shabgah A; Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran., Shekari N; Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran., Sehati N; Department of Genetic, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran., Hosseinzadeh R; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran., Mohammadi H; 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., Babaloo Z; 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.
Jazyk: angličtina
Zdroj: International journal of rheumatic diseases [Int J Rheum Dis] 2019 Apr; Vol. 22 (4), pp. 715-724. Date of Electronic Publication: 2019 Feb 10.
DOI: 10.1111/1756-185X.13494
Abstrakt: 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.
(© 2019 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)
Databáze: MEDLINE
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