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Susceptibility to ERAP1 gene single nucleotide polymorphism modulates the inflammatory cytokine setting in ankylosing spondylitis
Author(s) -
Hemmatzadeh Maryam,
Babaie Farhad,
Ezzatifar Fatemeh,
Mohammadi Fatemeh S.,
Ebrazeh Mehrdad,
Golabi Aghdam Shirin,
Hajaliloo Mehrzad,
Azizi Gholamreza,
Gowhari Shabgah Arezoo,
Shekari Najibeh,
Sehati Nasrin,
Hosseinzadeh Ramin,
Mohammadi Hamed,
Babaloo Zohreh
Publication year - 2019
Publication title -
international journal of rheumatic diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 41
eISSN - 1756-185X
pISSN - 1756-1841
DOI - 10.1111/1756-185x.13494
Subject(s) - single nucleotide polymorphism , genotyping , genotype , medicine , snp , microbiology and biotechnology , peripheral blood mononuclear cell , ankylosing spondylitis , polymerase chain reaction , odds ratio , immunology , gene , biology , genetics , in vitro
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.