Dataset Information

The IL17F His161Arg polymorphism, a potential risk locus for psoriasis, increases serum levels of interleukin-17F in an Asian population.

ABSTRACT: Interleukin 17 (IL-17) plays pivotal role in the pathogenesis of psoriasis. In a previous study, we identified a locus in the IL17F gene that is associated with psoriasis, the IL17F rs763780 (His161Arg) T/C variant. The current study aimed to elucidate the association between this polymorphism and psoriasis, and to determine its effect on serum levels of cytokine. A total of 116 psoriasis patients and 97 healthy volunteers were recruited. Genotyping analysis was performed using quantitative polymerase chain reaction, and serum levels of cytokine were measured using a multiplex immunoassay. The IL17F His161Arg polymorphism was significantly associated with psoriasis based on the genotype and allele analyses. Psoriasis patients harbouring the mutant allele had significantly increased serum levels of IL-17F. Our results suggest that this polymorphism is a potential risk locus for psoriasis and that it results in a direct increase in IL-17F production.

SUBMITTER: Choi BG

PROVIDER: S-EPMC6908672 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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The IL17F His161Arg polymorphism, a potential risk locus for psoriasis, increases serum levels of interleukin-17F in an Asian population.

Choi Byung Gon BG Hong Ji Youn JY Hong Joo Ran JR Hur Min Seok MS Kim Sung Min SM Lee Yang Won YW Choe Yong Beom YB Ahn Kyu Joong KJ

Scientific reports 20191212 1

Interleukin 17 (IL-17) plays pivotal role in the pathogenesis of psoriasis. In a previous study, we identified a locus in the IL17F gene that is associated with psoriasis, the IL17F rs763780 (His161Arg) T/C variant. The current study aimed to elucidate the association between this polymorphism and psoriasis, and to determine its effect on serum levels of cytokine. A total of 116 psoriasis patients and 97 healthy volunteers were recruited. Genotyping analysis was performed using quantitative poly ...[more]

PMID: 31831764

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Project description: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.

Project description:ImportanceHigh-cost biologic therapies have transformed the management of immune-mediated inflammatory diseases. To optimize outcomes and reduce costs, dose adjustment informed by measurement of circulating drug levels has been shown to be effective in various settings. However, limited evidence exists for this approach with the interleukin 12 and interleukin 23 inhibitor ustekinumab.ObjectiveTo evaluate clinical utility of therapeutic drug monitoring for ustekinumab in patients with psoriasis.Design, setting, and participantsA prospective observational cohort of 491 adults with psoriasis was recruited to the multicenter Biomarkers of Systemic Treatment Outcomes in Psoriasis study within the British Association of Dermatologists Biologic and Immunomodulators Register from June 2009 to December 2017; samples from some patients were taken between 2009 and 2011 as part of a pilot study with the same inclusion criteria.ExposureSerum ustekinumab level measured at any point during the dosing cycle using an enzyme-linked immunosorbent assay.Main outcomes and measuresDisease activity measured using the Psoriasis Area and Severity Index (PASI) score. Treatment response outcomes were PASI75 (75% reduction in PASI score from baseline [primary outcome]), PASI90 (90% reduction of PASI score from baseline), and absolute PASI score of 1.5 or less.ResultsA total of 491 patients (171 women and 320 men; mean [SD] age, 45.7 [12.8] years) had 1 or more serum samples (total, 853 samples obtained 0-56 weeks from start of treatment) and 1 or more PASI scores within the first year of treatment. Antidrug antibodies were detected in only 17 of 490 patients (3.5%). Early measured drug levels (1-12 weeks after starting treatment) were associated with PASI75 response 6 months after starting treatment (odds ratio, 1.38; 95% CI, 1.11-1.71) when adjusted for baseline PASI score, age, and ustekinumab dose. However, this finding was not consistent across the other PASI outcomes (PASI90 and PASI score of ≤1.5).Conclusions and relevanceThis real-world study provides evidence that measurement of early serum ustekinumab levels could be useful to direct the treatment strategy for psoriasis. Adequate drug exposure early in the treatment cycle may be particularly important in determining clinical outcome.

Dataset Information

The IL17F His161Arg polymorphism, a potential risk locus for psoriasis, increases serum levels of interleukin-17F in an Asian population.

Publications

The IL17F His161Arg polymorphism, a potential risk locus for psoriasis, increases serum levels of interleukin-17F in an Asian population.

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