Abstract
Psoriasis affects 2–3% of the population, causing significant morbidity and financial burden. Immunosuppressive drugs such as cyclosporine are first line systemic therapies for moderate-to-severe forms. However, patients exhibit heterogeneity in their response to therapy, possibly due to genetic factors. The aim of the present study was to assess the ABCB1 T-129C, G1199A, C1236T, G2677T and C3435T single-nucleotide polymorphisms (SNPs) as candidate predictive markers of response to cyclosporine treatment in 84 psoriasis patients. 62% of the patients were defined as responders and 38% as nonresponders. All SNPs complied with Hardy–Weinberg equilibrium. SNP and haplotype analyses were performed to access responsiveness to treatment. Association analysis revealed statistically significant association of SNP 3435 T with negative response (P=0.0075), a result that was further validated in haplotype analysis. This study is the first in the field of the pharmacogenetics of cyclosporine in psoriasis whose results merit further exploitation in larger independent cohorts.
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References
Bowcock AM, Krueger JG . Getting under the skin: the immunogenetics of psoriasis. Nat Rev Immunol 2005; 5: 699–711.
Lowes MA, Bowcock AM, Krueger JG . Pathogenesis and therapy of psoriasis. Nature 2007; 445: 866–873.
Prieto-Pérez R, Cabaleiro T, Daudén E, Ochoa D, Román M, Abad-Santos F . Pharmacogenetics of topical and systemic treatment of psoriasis. Pharmacogenomics 2013; 14: 1623–1634.
Vasilopoulos Y, Manolika M, Zafiriou E, Sarafidou T, Bagiatis V, Krüger-Krasagaki S et al. Pharmacogenetic analysis of TNF, TNFRSF1A and TNFRSF1B polymorphisms and prediction of response to anti-TNF therapy in psoriasis patients in the Greek population. Mol Diagn Ther 2012; 16: 29–34.
Tejasvi T, Stuart PE, Chandran V, Voorhees JJ, Gladman DD, Rahman P et al. TNFAIP3 gene polymorphisms are associated with response to TNF blockade in psoriasis. J Invest Dermatol 2012; 132: 593–600.
Kerb R . Implications of genetic polymorphisms in drug transporters for pharmacotherapy. Cancer Lett 2006; 234: 4–33.
Benet LZ, Cummins CL . The drug efflux-metabolism alliance: biochemical aspects. Adv Drug Deliv Rev 2001; 50 (Suppl 1): S3–S11.
Schwab M, Eichelbaum M, Fromm MF . Genetic polymorphisms of the human MDR1 drug transporter. Annu Rev Pharmacol Toxicol 2003; 43: 285–287.
Fanta S, Niemi M, Jönsson S, Karlsson MO, Holmberg C, Neuvonen PJ et al. Pharmacogenetics of cyclosporine in children suggests an age-dependent influence of ABCB1 polymorphisms. Pharmacogenet Genomics 2008; 18: 77–90.
Lin DY, Hu Y, Huang BE . Simple and efficient analysis of disease association with missing genotype data. Am J Hum Genet 2008; 82: 444–452.
Faul F, Erdfelder E, Buchner A, Lang AG . Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods 2009; 41: 1149–1160.
Gisondi P, Tessari G, Conti A, Piaserico S, Schianchi S, Peserico A et al. Prevalence of metabolic syndrome in patients with psoriasis: a hospital-based case-control study. Br J Dermatol 2007; 157: 68–73.
Wang D, Johnson AD, Papp AC, Kroetz DL, Sadée W . Multidrug resistance polypeptide 1 (MDR1, ABCB1) variant 3435C>T affects mRNA stability. Pharmacogenet Genomics 2005; 15: 693–704.
Lindell M, Karlsson MO, Lennernäs H, Påhlman L, Lang MA . Variable expression of CYP and Pgp genes in the human small intestine. Eur J Clin Invest 2003; 33: 493–499.
Hoffmeyer S, Burk O, von Richter O, Arnold HP, Brockmöller J, Johne A et al. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vitro. Proc Natl Acad Sci USA 2000; 97: 3473–3478.
Maiti AK, Nath SK . Gene network analysis of small molecules with autoimmune disease associated genes predicts a novel strategy for drug efficacy. Autoimmun Rev 2013; 12: 510–522.
Acknowledgements
We are very grateful to all the participants of the study. This work was supported by the postgraduate programs ‘Biotechnology-Quality Assessment in Nutrition and the Environment’ and ‘Molecular Biology and Genetics Applications—Diagnostic Markers’ of the Department of Biochemistry and Biotechnology, University of Thessaly, Greece.
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Vasilopoulos, Y., Sarri, C., Zafiriou, E. et al. A pharmacogenetic study of ABCB1 polymorphisms and cyclosporine treatment response in patients with psoriasis in the Greek population. Pharmacogenomics J 14, 523–525 (2014). https://doi.org/10.1038/tpj.2014.23
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DOI: https://doi.org/10.1038/tpj.2014.23
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