Background: Psoriasis is characterized by multiple genetic variations. Some of these variations, such as the presence of HLA-Cw6 or TNFAIP3 single-nucleotide polymorphisms (SNPs), have been correlated to the response to biologic treatments. Objective: The aim of our study was to evaluate the effects of IL12B and IL6 SNPs on the response to ustekinumab. Methods: We retrospectively analyzed the genotypes of 64 patients who had been treated with ustekinumab for up to 1 year. Efficacy data were evaluated using ‘intention to treat-last observation carried forward' analysis. Results: We confirmed the positive role of HLA-Cw6 as a predictor of the response to ustekinumab and discovered that presence of the GG genotype on the IL12B rs6887695 SNP and absence of the AA genotype on the IL12B rs3212227 SNP significantly increase the probability of therapeutic success in HLA-Cw6 positive patients. Conclusions: The availability of pharmacogenetic data will influence therapeutic decisions in the clinical management of psoriatic patients.

1.
Jacobson CC, Kumar S, Kimball AB: Latitude and psoriasis prevalence. J Am Acad Dermatol 2011;65:870-873.
2.
Saraceno R, Mannheimer R, Chimenti S: Regional distribution of psoriasis in Italy. J Eur Acad Dermatol Venereol 2008;22:324-329.
3.
Cargill M, Schrodi SJ, Chang M, Garcia VE, Brandon R, Callis KP, Matsunami N, Ardlie KG, Civello D, Catanese JJ, Leong DU, Panko JM, McAllister LB, Hansen CB, Papenfuss J, Prescott SM, White TJ, Leppert MF, Krueger GG, Begovich AB: A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. Am J Hum Genet 2007;80:273-290.
4.
Kurd SK, Troxel AB, Crits-Christoph P, Gelfand JM: The risk of depression, anxiety, and suicidality in patients with psoriasis: a population-based cohort study. Arch Dermatol 2010;146:891-895.
5.
Catanoso M, Pipitone N, Salvarani C: Epidemiology of psoriatic arthritis. Reumatismo 2012;64:66-70.
6.
Armstrong AW, Schupp C, Bebo B: Psoriasis comorbidities: results from the National Psoriasis Foundation surveys 2003 to 2011. Dermatology 2012;225:121-126.
7.
Griffiths CE, Barker JN: Pathogenesis and clinical features of psoriasis. Lancet 2007;370:263-271.
8.
Lowes MA, Bowcock AM, Krueger JG: Pathogenesis and therapy of psoriasis. Nature 2007;445:866-873.
9.
Oestreicher JL, Walters IB, Kikuchi T, Gilleaudeau P, Surette J, Schwertschlag U, Dorner AJ, Krueger JG, Trepicchio WL: Molecular classification of psoriasis disease-associated genes through pharmacogenomic expression profiling. Pharmacogenomics J 2001;1:272-287.
10.
Boca AN, Talamonti M, Galluzzo M, Botti E, Vesa SC, Chimenti S, Buzoianu AD, Costanzo A: Genetic variations in IL6 and IL12B decreasing the risk for psoriasis. Immunol Lett 2013;156:127-131.
11.
Elder JT, Bruce AT, Gudjonsson JE, Johnston A, Stuart PE, Tejasvi T, Voorhees JJ, Abecasis GR, Nair RP: Molecular dissection of psoriasis: integrating genetics and biology. J Invest Dermatol 2010;130:1213-1226.
12.
Duffin KC, Krueger GG: Genetic variations in cytokines and cytokine receptors associated with psoriasis found by genome-wide association. J Invest Dermatol 2009;129:827-833.
13.
Di Cesare A, Di Meglio P, Nestle FO: The IL-23/Th17 axis in the immunopathogenesis of psoriasis. J Invest Dermatol 2009;129:1339-1350.
14.
Zhu KJ, Zhu CY, Shi G, Fan YM: Meta-analysis of IL12B polymorphisms (rs3212227, rs6887695) with psoriasis and psoriatic arthritis. Rheumatol Int 2013;33:1785-1790.
15.
Nair RP, Ruether A, Stuart PE, Jenisch S, Tejasvi T, Hiremagalore R, Schreiber S, Kabelitz D, Lim HW, Voorhees JJ, Christophers E, Elder JT, Weichenthal M: Susceptibility-associated genetic variation at IL12B enhances Th1 polarization in psoriasis. J Invest Dermatol 2008;128:1653-1661.
16.
Johnston A, Xing X, Swindell WR, Kochkodan J, Riblett M, Nair RP, Stuart PE, Ding J, Voorhees JJ, Elder JT, Gudjonsson JE: Susceptibility-associated genetic variation at IL12B enhances Th1 polarization in psoriasis. Hum Mol Genet 2013;22:1807-1815.
17.
Suttle MM, Nilsson G, Snellman E, Harvima IT: Experimentally induced psoriatic lesion associates with interleukin (IL)-6 in mast cells and appearance of dermal cells expressing IL-33 and IL-6 receptor. Clin Exp Immunol 2012;169:311-319.
18.
Goodman WA, Levine AD, Massari JV, Sugiyama H, McCormick TS, Cooper KD: IL-6 signaling in psoriasis prevents immune suppression by regulatory T cells. J Immunol 2009;183:3170-3176.
19.
O'Rielly DD, Rahman P: Pharmacogenetics of psoriasis. Pharmacogenomics 2011;12:87-101.
20.
Foulkes AC, Warren RB: Pharmacogenomics and the resulting impact on psoriasis therapies. Dermatol Clin 2015;33:149-160.
21.
Hébert HL, Ali FR, Bowes J, Griffiths CE, Barton A, Warren RB: Genetic susceptibility to psoriasis and psoriatic arthritis: implications for therapy. Br J Dermatol 2012;166:474-482.
22.
Woolf RT, Smith CH: How genetic variation affects patient response and outcome to therapy for psoriasis. Expert Rev Clin Immunol 2010;6:957-966.
23.
Ryan C, Menter A, Warren RB: The latest advances in pharmacogenetics and pharmacogenomics in the treatment of psoriasis. Mol Diagn Ther 2010;14:81-93.
24.
Ameen M: Genetic basis of psoriasis vulgaris and its pharmacogenetic potential. Pharmacogenomics 2003;4:297-308.
25.
Suárez-Fariñas M, Shah KR, Haider AS, Krueger JG, Lowes MA: Personalized medicine in psoriasis: developing a genomic classifier to predict histological response to Alefacept. BMC Dermatol 2010;10:1.
26.
Talamonti M, Botti E, Galluzzo M, Teoli M, Spallone G, Bavetta M, Chimenti S, Costanzo A: A Pharmacogenetics of psoriasis: HLA-Cw6 but not LCE3B/3C deletion nor TNFAIP3 polymorphism predisposes to clinical response to interleukin 12/23 blocker ustekinumab. Br J Dermatol 2013;169:458-463.
27.
Chiu HY, Wang TS, Chan CC, Cheng YP, Lin SJ, Tsai TF: Human leucocyte antigen-Cw6 as a predictor for clinical response to ustekinumab, an interleukin-12/23 blocker, in Chinese patients with psoriasis: a retrospective analysis. Br J Dermatol 2014;171:1181-1188.
28.
Tejasvi T, Stuart PE, Chandran V, et al: TNFAIP3 gene polymorphisms are associated with response to TNF blockade in psoriasis. J Invest Dermatol 2012;132:593-600.
29.
Gallo E, Cabaleiro T, Román M, Solano-López G, Abad-Santos F, García-Díez A, Daudén E: The relationship between tumour necrosis factor (TNF)-α promoter and IL12B/IL-23R genes polymorphisms and the efficacy of anti-TNF-α therapy in psoriasis: a case-control study. Br J Dermatol 2013;169:819-829.
30.
Di Renzo L, Bianchi A, Saraceno R, Calabrese V, Cornelius C, Iacopino L, Chimenti S, De Lorenzo A: -174G/C IL-6 gene promoter polymorphism predicts therapeutic response to TNF-α blockers. Pharmacogenet Genomics 2012;22:134-142.
31.
Kristiansen OP, Nolsøe RL, Larsen L, Gjesing AM, Johannesen J, Larsen ZM, Lykkesfeldt AE, Karlsen AE, Pociot F, Mandrup-Poulsen T; DIEGG; DSGD: Association of a functional 17beta-estradiol sensitive IL6-174G/C promoter polymorphism with early-onset type 1 diabetes in females. Hum Mol Genet 2003;12:1101-1110.
32.
de Cid R, Riveira-Munoz E, Zeeuwen PL, Robarge J, Liao W, Dannhauser EN, Giardina E, Stuart PE, Nair R, Helms C, Escaramís G, Ballana E, Martín-Ezquerra G, den Heijer M, Kamsteeg M, Joosten I, Eichler EE, Lázaro C, Pujol RM, Armengol L, Abecasis G, Elder JT, Novelli G, Armour JA, Kwok PY, Bowcock A, Schalkwijk J, Estivill X: Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility factor for psoriasis. Nat Genet 2009;41:211-215.
33.
Singh RP, Hasan S, Sharma S, Nagra S, Yamaguchi DT, Wong DT, Hahn BH, Hossain A: Th17 cells in inflammation and autoimmunity. Autoimmun Rev 2014;13:1174-1181.
34.
Johnston A, Xing X, Swindell WR, Kochkodan J, Riblett M, Nair RP, Stuart PE, Ding J, Voorhees JJ, Elder JT, Gudjonsson JE: Susceptibility-associated genetic variation at IL12B enhances Th1 polarization in psoriasis. Hum Mol Genet 2013;22:1807-1815.
35.
Huth C, Heid IM, Vollmert C, Gieger C, Grallert H, Wolford JK, Langer B, Thorand B, Klopp N, Hamid YH, Pedersen O, Hansen T, Lyssenko V, Groop L, Meisinger C, Döring A, Löwel H, Lieb W, Hengstenberg C, Rathmann W, Martin S, Stephens JW, Ireland H, Mather H, Miller GJ, Stringham HM, Boehnke M, Tuomilehto J, Boeing H, Möhlig M, Spranger J, Pfeiffer A, Wernstedt I, Niklason A, López-Bermejo A, Fernández-Real JM, Hanson RL, Gallart L, Vendrell J, Tsiavou A, Hatziagelaki E, Humphries SE, Wichmann HE, Herder C, Illig T: IL6 gene promoter polymorphisms and type 2 diabetes: joint analysis of individual participants' data from 21 studies. Diabetes 2006;55:2915-2921.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.