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Abstract
Ankylosing spondylitis (AS) is a chronic autoimmune inflammatory disease that mainly affects the axial and sacroiliac joints. Single-nucleotide polymorphisms (SNPs) in genes encoding cytokines have been associated with AS, which can interfere with the production of these cytokines and contribute to the development of AS. In order to contribute to a better understanding of the pathology of AS, our objective was to investigate a possible association of the IL10 −1082 A>G SNP (rs1800896) with AS and to evaluate the serum levels of TNF-α, IL-10, IL-17A, and IL-17F in AS patients and controls comparing them with their respective genotypes (TNF rs1800629, IL10 rs1800896, IL17A rs2275913, and IL17F rs763780). Patients and controls were selected from the Maringá University Hospital and the Maringá Rheumatism Clinic, in Paraná State, Southern Brazil, and they were diagnosed by the ASAS Criteria. In total, 149 patients and 169 controls were genotyped for the IL10 −1082 A>G polymorphism using a polymerase chain reaction with sequence specific primers (PCR-SSP); the measurement of TNF-α serum levels was performed through the immunofluorimetric test and IL-10, IL-17A, and IL-17F using an ELISA test. There was a high frequency of the IL10 −1082 G allele in AS patients compared with controls with an odds ratio of 1.83 and 95% confidence interval of 1.32 to 2.54, and a significant difference in the genotype frequencies of the IL10 −1082 A/G+G/G between patients and healthy controls, with an odds ratio of 3.01 and 95% confidence interval of 1.75 to 5.17. In addition, increased serum levels of IL-10 were observed in AS patients: 2.38 (IQR, 0.91) pg/ml compared with controls 1.72 (IQR 0.93) pg/ml (P = 0.01). Our results also showed an association between IL17F rs763780 C/T+T/T genotypes and increased serum levels of IL-17F in patients with AS and also in controls. We can conclude that patients with the A/G and G/G genotypes for −1082 A>G (rs1800896) in the IL10 gene are three times more likely to develop AS, that the serum level of IL-10 was higher in AS patients and that the IL17F rs763780 polymorphism can affect the levels of IL-17F in the serum of patients and controls in the same way.
Highlights
Ankylosing spondylitis (AS) is a chronic autoimmune inflammatory disease that mainly affects the axial and sacroiliac joints, causing severe pain
In order to contribute to a better understanding of the pathology of AS, our objective was to investigate a possible association of the IL10 −1082 A>G single nucleotide polymorphisms (SNPs) with AS and to evaluate the serum levels of tumour necrosis factor alpha (TNF-a), IL-10, IL-17A, and IL-17F in AS patients and controls comparing them with their respective genotypes (TNF rs1800629, IL10 rs1800896, IL17A rs2275913, and IL17F rs763780)
In order to elucidate the pathology of AS and identify new genetic markers, we investigated a possible association of the IL10 SNP −1082 A>G with AS, and evaluated the serum levels of TNF-a, IL-10, IL-17A, and IL-17F in AS patients and controls compared with their respective genotypes (TNF rs1800629, IL17A rs2275913, IL17F rs763780, and IL10 rs1800896)
Summary
Ankylosing spondylitis (AS) is a chronic autoimmune inflammatory disease that mainly affects the axial and sacroiliac joints, causing severe pain. Polymorphisms located in the 5′-flanking region of the IL10 gene, at positions −1082 A>G, −819 T>C, and −592 A>C, are known to be involved in regulating the production of IL-10, with the first being the best characterised of them [5]. Three single nucleotide polymorphisms (SNPs) in genes that encode inflammatory cytokines have been associated with AS, in a previous study by our research group (TNF rs1800629, IL17A rs2275913, and IL17F rs763780) [6]. These polymorphisms can interfere with the level of production of these cytokines and contribute to the development of AS [7,8,9,10]
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