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The TNFRSF1B rs1061622 polymorphism (p.M196R) is associated with biological drug outcome in Psoriasis patients

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Abstract

Genetic factors are involved not only in the overall risk of suffering psoriasis, but also in their clinical characteristics and eventually in drug outcome. Biological therapies have dramatically improved the prognosis of Psoriasis. However, these treatments are very expensive and patients often exhibit a heterogeneous response that could be partially attributed to their genetic background. Thus, the research for genetic markers in psoriatic patients that could predict a poor response to biological therapies is an important issue. Our aim was to evaluate the effect of DNA variants at the “TNFα pathway” that could affect the risk of developing Psoriasis or the response to biological therapies among these patients. The genetic association study included a total of 518 Psoriatic patients and 480 healthy controls. Ninety of these patients received biological treatment and based on the change in the PASI score after 24 weeks were classified as good (PASI score ≥75 %), intermediate (PASI 50–75), and non-responders (PASI <50). Next generation sequencing (NGS) with semiconductor-array technology was used to identify the nucleotide variants in the TNF α, TNFRSF1A and TNFRSF1B, and we only found three missense amino acid changes, all in TNFRSF1B. Interestingly, we found a significantly higher frequency of rs1061622 G carriers among CW6-positive patients (p = 0.004; OR = 1.69, 95 % CI = 1.18–2.41). Allele G (p.196R) carriers were significantly more frequent in the non-responder group (56 %) (p = 0.05). In conclusion, we report a significant association between the TNFRSF1B p.M196R variant and the risk for psoriasis and the response to treatment with anti-TNF or anti-Il-12/Il-23. The genotyping of this polymorphism could help to optimize the treatment by identifying patients with a likely poor response to biological drugs.

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Acknowledgments

This work was supported by a grant from the Spanish Instituto de Salud Carlos III-European FEDER founds (Grant PI 13/00680). Authors thank ABBVIE for supporting this work. We thank Belén Alonso for technical assistance.

Conflict of interest

P. Coto-Segura is an invited speaker for and receives grant/research support from Abbvie, Janssen-Cilag, Schering-Plough, Pfizer 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. No writing assistance was utilized in the production of this manuscript. Other authors declare no conflict of interest.

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    Authors and Affiliations

    1. Unit of Psoriasis, Dermatology II Department, Hospital Universitario Central de Asturias, University of Oviedo, 33006, Oviedo, Spain

      Leire González-Lara, Ana Batalla, Noemí Eiris, Jorge Santos-Juanes & Pablo Coto-Segura

    2. Molecular Genetics Department, Hospital Universitario Central Asturias, Oviedo, Spain

      Eliecer Coto & Juan Gómez

    3. Reumathology Department, Hospital Universitario Central Asturias, Oviedo, Spain

      Rubén Queiro

    4. Medicine Department, University of Oviedo, Oviedo, Spain

      Eliecer Coto & Pablo Coto-Segura

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    1. Leire González-Lara
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    2. Ana Batalla
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    Correspondence to Leire González-Lara.

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    Leire González-Lara and Ana Batalla had contributed equally to this work.

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    González-Lara, L., Batalla, A., Coto, E. et al. The TNFRSF1B rs1061622 polymorphism (p.M196R) is associated with biological drug outcome in Psoriasis patients. Arch Dermatol Res 307, 405–412 (2015). https://doi.org/10.1007/s00403-014-1533-z

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    • DOI: https://doi.org/10.1007/s00403-014-1533-z

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