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IL17RA gene variants and anti-TNF response among psoriasis patients

The Pharmacogenomics Journal volume 18, pages 76–80 (2018)Cite this article

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Abstract

Polymorphisms at genes encoding proteins involved in the pathogenesis of psoriasis (Psor) or in the mechanism of action of biological drugs could influence the treatment response. Because the interleukin (IL)-17 family has a central role in the pathogenesis of Psor, we hypothesized that IL17RA variants could influence the response to anti-TNF drugs among Psor patients. To address this issue we performed a cross-sectional study of Psor patients who received the biological treatments for the first time, with a follow-up of at least 6 months. All of the patients were Caucasian, older than 18 years old, with chronic plaque Psor, and had completed at least 24 weeks of anti-TNF therapy (adalimumab, etanercept or infliximab). The treatment response to anti-TNF agents was evaluated according to the achievement of PASI50 and PASI75 at weeks 12 and 24. Those who achieved PASI75 at week 24 were considered good responders. All patients were genotyped for the selected single-nucleotide polymorphisms (SNPs) at IL17RA gene. A total of 238 patients were included (57% male, mean age 46 years). One hundred and five patients received adalimumab, 91 patients etanercept and 42 infliximab. The rs4819554 promoter SNP allele A was significantly more common among responders at weeks 12 (P=0.01) and 24 (P=0.04). We found a higher frequency of AA versus AG+GG among responders, but the difference was only significant at week 12 (P=0.03, odd ratio=1.86, 95% confidence of interval=1.05–3.27). Thus, in the study population, the SNP rs4819554 in the promoter region of IL17RA significantly influences the response to anti-TNF drugs at week 12.

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Acknowledgements

This work was supported by a grant from the Spanish Instituto de Salud Carlos III-European FEDER founds (Grants PI 13/00680 and PI10/01740). We thank Teresa Cabaleiro (PhD), Dolores Ochoa (MD, PhD), Manuel Román (Technician) and María Talegón (Technician) for technical assistance.

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The funding was not involved in any aspects of the manuscript elaboration (design, collection, management, analysis or interpretation of data, preparation, review or approval, decision to submit for publication).

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Authors and Affiliations

  1. Department of Dermatology II; Hospital Universitario Central Asturias,

    A Batalla, N Eirís, D González-Fernández, C Gómez-De Castro & P Coto-Segura

  2. Hospital Universitario Central Asturias, Oviedo, Spain

    A Batalla, N Eirís, D González-Fernández, C Gómez-De Castro & P Coto-Segura

  3. Department of Molecular Genetics, Hospital Universitario Central Asturias, Oviedo, Spain

    E Coto, J Gómez, L F Cardo, B Alonso & S Iglesias

  4. Department of Dermatology, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain

    E Daudén & M Llamas-Velasco

  5. Department of Clinical Pharmacology, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, University Autónoma de Madrid (UAM), Instituto de Investigación Sanitaria la Princesa (IP), Madrid, Spain

    R Prieto-Perez & F Abad-Santos

  6. Department of Dermatology, HU Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria, Spain

    G Carretero

  7. Department of Immunology, HU Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria, Spain

    F S García

  8. Unidad Investigación HU Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria, Spain

    Y B Godoy

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Correspondence to P Coto-Segura.

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Competing interests

Dr Coto-Segura is an invited speaker for and receives grant/research support from Abbvie, Janssen-Cilag, Schering-Plough, Pfizer, Celgene and Novartis. The author have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Dr Daudén has the following conflict of interests: Advisory Board member, consultant, grants, research support, participation in clinical trials and receives honorarium for speaking, with the following pharmaceutical companies: Abbvie/Abbott, Amgen, Janssen-Cilag, LeoPharma, Novartis, Pfizer, MSD-Schering-Plough, Celgene, Lilly. Dr Batalla has participated in clinical trials of Novartis and LeoPharma. Dr Abad-Santos has been a consultant or investigator in clinical trials sponsored by the following pharmaceutical companies: Abbott, Alter, Chemo, Cinfa, Farmalíder, Ferrer, GlaxoSmithKline, Gilead, Janssen-Cilag, Kern, Normon, Novartis, Servier, Teva, and Zambon. Other authors declare no conflict of interest.

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Batalla, A., Coto, E., Gómez, J. et al. IL17RA gene variants and anti-TNF response among psoriasis patients. Pharmacogenomics J 18, 76–80 (2018). https://doi.org/10.1038/tpj.2016.70

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