{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T17:02:52Z","timestamp":1770742972715,"version":"3.49.0"},"reference-count":58,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,3,17]],"date-time":"2024-03-17T00:00:00Z","timestamp":1710633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Moderate-to-severe psoriasis (Ps) treatment includes systemic drugs and biological agents. Apremilast, a small molecule primarily metabolized by cytochrome CYP3A4, modulates the immune system by specifically inhibiting phosphodiesterase type 4 (PDE4) isoforms and is currently used for the treatment of Ps and psoriatic arthritis (PsA). Clinical trials and real-world data showed variable efficacy in response among Ps patients underlying the need for personalized therapy. This study implements a candidate-gene and a network-based approach to identify genetic markers associated with apremilast response in forty-nine Greek Ps patients. Our data revealed an association of sixty-four SNPs within or near PDE4 and CYP3A4 genes, four SNPs in ncRNAs ANRIL, LINC00941 and miR4706, which influence the abundance or function of PDE4s, and thirty-three SNPs within fourteen genes whose protein products either interact directly with PDE4 proteins or constitute components of the cAMP signaling pathway which is modulated by PDE4s. Notably, fifty-six of the aforementioned SNPs constitute eQTLs for the respective genes in relevant to psoriasis tissues\/cells implying that these variants could be causal. Our analysis provides a number of novel genetic variants that, upon validation in larger cohorts, could be utilized as predictive markers regarding the response of Ps patients to apremilast treatment.<\/jats:p>","DOI":"10.3390\/genes15030369","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T05:14:07Z","timestamp":1710738847000},"page":"369","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["PDE4 Gene Family Variants Are Associated with Response to Apremilast Treatment in Psoriasis"],"prefix":"10.3390","volume":"15","author":[{"given":"Kalliopi","family":"Liadaki","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Biotechnology, University of Thessaly, Viopolis, 41500 Larissa, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Efterpi","family":"Zafiriou","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Viopolis, 41500 Larissa, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1842-5432","authenticated-orcid":false,"given":"Themistoklis","family":"Giannoulis","sequence":"additional","affiliation":[{"name":"Department of Animal Science, University of Thessaly, Gaiopolis, 41334 Larissa, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofia","family":"Alexouda","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biotechnology, University of Thessaly, Viopolis, 41500 Larissa, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kleoniki","family":"Chaidaki","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Viopolis, 41500 Larissa, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Polyxeni","family":"Gidarokosta","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Viopolis, 41500 Larissa, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angeliki-Viktoria","family":"Roussaki-Schulze","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Viopolis, 41500 Larissa, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8900-7281","authenticated-orcid":false,"given":"Sotirios G.","family":"Tsiogkas","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Viopolis, 41500 Larissa, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4733-2585","authenticated-orcid":false,"given":"Athina","family":"Daponte","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Viopolis, 41500 Larissa, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6868-8927","authenticated-orcid":false,"given":"Zissis","family":"Mamuris","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biotechnology, University of Thessaly, Viopolis, 41500 Larissa, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9697-7902","authenticated-orcid":false,"given":"Dimitrios P.","family":"Bogdanos","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Viopolis, 41500 Larissa, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2556-537X","authenticated-orcid":false,"given":"Nicholas K.","family":"Moschonas","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Patras, 26500 Patras, Greece"},{"name":"Foundation for Research and Technology Hellas, Institute of Chemical Engineering Sciences, 26504 Patras, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theologia","family":"Sarafidou","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biotechnology, University of Thessaly, Viopolis, 41500 Larissa, 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(2023). Challenges and Future Trends in the Treatment of Psoriasis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241713313"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Wang, C.-Y., Wang, C.-W., Chen, C.-B., Chen, W.-T., Chang, Y.-C., Hui, R.C.-Y., and Chung, W.-H. (2023). Pharmacogenomics on the Treatment Response in Patients with Psoriasis: An Updated Review. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24087329"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s40257-017-0322-9","article-title":"Pharmacogenetics and Pharmacogenomics in Moderate-to-Severe Psoriasis","volume":"19","author":"Reolid","year":"2018","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e12760","DOI":"10.1111\/dth.12760","article-title":"Secondary failure of TNF-\u03b1 inhibitors in clinical practice","volume":"32","author":"Owczarek","year":"2019","journal-title":"Dermatol. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1007\/s13555-022-00693-2","article-title":"Biologic Therapy for Moderate to Severe Psoriasis. Real-World Follow-up of Patients Who Initiated Biologic Therapy at Least 10 Years Ago","volume":"12","author":"Paradela","year":"2022","journal-title":"Dermatol. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e14261","DOI":"10.1111\/dth.14261","article-title":"Apremilast in dermatology: A review of literature","volume":"33","author":"Nassim","year":"2020","journal-title":"Dermatol. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1586\/1744666X.2016.1134319","article-title":"A new therapeutic for the treatment of moderate-to-severe plaque psoriasis: Apremilast","volume":"12","author":"Chiricozzi","year":"2016","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Johnson, K.R., Nicodemus-Johnson, J., and Danziger, R.S. (2010). An evolutionary analysis of cAMP-specific Phosphodiesterase 4 alternative splicing. BMC Evol. Biol., 10.","DOI":"10.1186\/1471-2148-10-247"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1016\/j.cellsig.2014.05.014","article-title":"Apremilast is a selective PDE4 inhibitor with regulatory effects on innate immunity","volume":"26","author":"Schafer","year":"2014","journal-title":"Cell Signal."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1007\/s40265-017-0709-1","article-title":"Apremilast: A Review in Psoriasis and Psoriatic Arthritis","volume":"77","author":"Keating","year":"2017","journal-title":"Drugs"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.pharmthera.2012.12.007","article-title":"Cytochrome P450 enzymes in drug metabolism: Regulation of gene expression, enzyme activities, and impact of genetic variation","volume":"138","author":"Zanger","year":"2013","journal-title":"Pharmacol. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.jaad.2015.03.049","article-title":"Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1)","volume":"73","author":"Papp","year":"2015","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1111\/bjd.14164","article-title":"Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate-to-severe plaque psoriasis over 52 weeks: A phase III, randomized controlled trial (ESTEEM 2)","volume":"173","author":"Paul","year":"2015","journal-title":"Br. J. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1111\/jdv.14738","article-title":"Safety and efficacy of apremilast through 104 weeks in patients with moderate to severe psoriasis who continued on apremilast or switched from etanercept treatment: Findings from the LIBERATE study","volume":"32","author":"Reich","year":"2018","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1111\/ced.13150","article-title":"Real-world, single-centre experience of apremilast for the treatment of moderate to severe psoriasis","volume":"42","author":"Wong","year":"2017","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1111\/jdv.14832","article-title":"Real-world data on the effectiveness and safety of apremilast in patients with moderate-to-severe plaque psoriasis","volume":"32","author":"Papadavid","year":"2018","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1177\/1203475418755982","article-title":"Efficacy and safety of apremilast monotherapy for moderate to severe psoriasis: Retrospective study","volume":"22","author":"Ighani","year":"2018","journal-title":"J. Cutan. Med. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Verbenko, D.A., Karamova, A.E., Artamonova, O.G., Deryabin, D.G., Rakitko, A., Chernitsov, A., Krasnenko, A., Elmuratov, A., Solomka, V.S., and Kubanov, A.A. (2020). Apremilast Pharmacogenomics in Russian Patients with Moderate-to-Severe and Severe Psoriasis. J. Pers. Med., 11.","DOI":"10.3390\/jpm11010020"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"D933","DOI":"10.1093\/nar\/gkac958","article-title":"Ensembl 2023","volume":"51","author":"Martin","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: A tool set for whole-genome association and population-based linkage analyses","volume":"81","author":"Purcell","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"D140","DOI":"10.1093\/nar\/gky1051","article-title":"LncRNA2Target v2.0: A comprehensive database for target genes of lncRNAs in human and mouse","volume":"47","author":"Cheng","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"D222","DOI":"10.1093\/nar\/gkab1079","article-title":"miRTarBase update 2022: An informative resource for experimentally validated miRNA\u2013target interactions","volume":"50","author":"Huang","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1093\/bioinformatics\/btaa1070","article-title":"PICKLE 3.0: Enriching the human meta-database with the mouse protein interactome extended via mouse\u2013human orthology","volume":"37","author":"Dimitrakopoulos","year":"2020","journal-title":"Bioinformatics"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Dimitrakopoulos, G.N., Klapa, M.I., and Moschonas, N.K. (2022). How Far Are We from the Completion of the Human Protein Interactome Reconstruction?. Biomolecules, 12.","DOI":"10.3390\/biom12010140"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Berna-Rico, E., Perez-Bootello, J., Abbad-Jaime de Aragon, C., and Gonzalez-Cantero, A. (2023). Genetic Influence on Treatment Response in Psoriasis: New Insights into Personalized Medicine. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24129850"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1080\/14712598.2021.1862082","article-title":"HLA-Cw6 and other HLA-C alleles, as well as MICBDT, DDX58, and TYK2 genetic variants associate with optimal response to anti-IL-17A treatment in patients with psoriasis","volume":"21","author":"Morelli","year":"2021","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/j.ajhg.2015.10.019","article-title":"Genome-wide Association Analysis of Psoriatic Arthritis and Cutaneous Psoriasis Reveals Differences in Their Genetic Architecture","volume":"97","author":"Stuart","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6046","DOI":"10.1038\/ncomms7046","article-title":"Dense genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis","volume":"6","author":"Bowes","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6916","DOI":"10.1038\/ncomms7916","article-title":"Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility","volume":"6","author":"Yin","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Allanore, Y., Saad, M., Dieud\u00e9, P., Avouac, J., Distler, J.H., Amouyel, P., Matucci-Cerinic, M., Riemekasten, G., Airo, P., and Melchers, I. (2011). Genome-wide scan identifies TNIP1, PSORS1C1, and RHOB as novel risk loci for systemic sclerosis. PLoS Genet., 7.","DOI":"10.1371\/journal.pgen.1002091"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1038\/ng.3359","article-title":"Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations","volume":"47","author":"Liu","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41439-018-0033-7","article-title":"Genetics of narcolepsy","volume":"6","author":"Miyagawa","year":"2019","journal-title":"Hum. Genome Var."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.neurobiolaging.2020.04.025","article-title":"Genome-wide interaction analysis of pathological hallmarks in Alzheimer\u2019s disease","volume":"93","author":"Wang","year":"2020","journal-title":"Neurobiol. Aging"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"11063","DOI":"10.1038\/srep11063","article-title":"DNA methylation at IL32 in juvenile idiopathic arthritis","volume":"5","author":"Meyer","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1111\/jns.12484","article-title":"Variations within Toll-like receptor (TLR) and TLR signaling pathway-related genes and their synergistic effects on the risk of Guillain-Barr\u00e9 syndrome","volume":"27","author":"Dutta","year":"2022","journal-title":"J. Peripher. Nerv. Syst."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1111\/sji.12251","article-title":"Association of NFKB1 and NFKBIA polymorphisms in relation to susceptibility of Beh\u00e7et\u2019s disease","volume":"81","author":"Yenmis","year":"2015","journal-title":"Scand. J. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1111\/apt.15187","article-title":"Polymorphisms in the NFkB, TNF-alpha, IL-1beta, and IL-18 pathways are associated with response to anti-TNF therapy in Danish patients with inflammatory bowel disease","volume":"49","author":"Bank","year":"2019","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1007\/s12031-018-1069-3","article-title":"Association study of ANRIL genetic variants and multiple sclerosis","volume":"65","author":"Rezazadeh","year":"2018","journal-title":"J. Mol. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"106053","DOI":"10.1016\/j.intimp.2019.106053","article-title":"Genetic variants within ANRIL (antisense non-coding RNA in the INK4 locus) are associated with risk of psoriasis","volume":"78","author":"Rakhshan","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1684\/ejd.2022.4240","article-title":"ANRIL polymorphisms in psoriasis vulgaris patients in northern China","volume":"32","author":"Hao","year":"2022","journal-title":"Eur. J. Dermatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4516","DOI":"10.1093\/hmg\/ddt299","article-title":"The large non-coding RNA ANRIL, which is associated with atherosclerosis, periodontitis and several forms of cancer, regulates ADIPOR1, VAMP3 and C11ORF10","volume":"22","author":"Bochenek","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e46612","DOI":"10.15252\/embr.201846612","article-title":"The long non-coding RNA LINC00941 and SPRR5 are novel regulators of human epidermal homeostasis","volume":"20","author":"Ziegler","year":"2019","journal-title":"EMBO Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.ncrna.2020.12.003","article-title":"Regulation of TGF\u03b2\/SMAD signaling by long non-coding RNAs in different cancers: Dark Knight in the Castle of molecular oncology","volume":"6","author":"Adylova","year":"2021","journal-title":"Noncoding RNA Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1038\/nature03966","article-title":"The protein kinase A anchoring protein mAKAP coordinates two integrated cAMP effector pathways","volume":"437","author":"Soughayer","year":"2005","journal-title":"Nature"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1152\/physiol.00041.2008","article-title":"AKAP-scaffolding proteins and regulation of cardiac physiology","volume":"24","author":"Mauban","year":"2009","journal-title":"Physiology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e016615","DOI":"10.1161\/JAHA.120.016615","article-title":"AKAP12 Signaling Complex: Impacts of Compartmentalizing cAMP-Dependent Signaling Pathways in the Heart and Various Signaling Systems","volume":"9","author":"Qasim","year":"2020","journal-title":"J. Am. Heart Assoc."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3264","DOI":"10.1016\/j.febslet.2005.03.089","article-title":"Compartmentalisation of phosphodiesterases and protein kinase A: Opposites attract","volume":"579","author":"Baillie","year":"2005","journal-title":"FEBS Lett."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/s11010-011-0911-5","article-title":"Novel human BTB\/POZ domain-containing zinc finger protein ZBTB1 inhibits transcriptional activities of CRE","volume":"357","author":"Liu","year":"2011","journal-title":"Mol. Cell Biochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"6413","DOI":"10.4049\/jimmunol.1001829","article-title":"The role of the transcription factor CREB in immune function","volume":"185","author":"Wen","year":"2010","journal-title":"J. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1006\/excr.2002.5491","article-title":"Coupling cAMP signaling to transcription in the liver: Pivotal role of CREB and CREM","volume":"275","author":"Servillo","year":"2002","journal-title":"Exp. Cell Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1021\/bi901948j","article-title":"Molecular mechanisms of system control of NF-kappaB signaling by IkappaBalpha","volume":"49","author":"Ferreiro","year":"2010","journal-title":"Biochemistry"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1097\/FPC.0000000000000183","article-title":"CYP3A4 intronic SNP rs35599367 (CYP3A4*22) alters RNA splicing","volume":"26","author":"Wang","year":"2016","journal-title":"Pharmacogenet. Genom."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1038\/tpj.2010.28","article-title":"Intronic polymorphism in CYP3A4 affects hepatic expression and response to statin drugs","volume":"11","author":"Wang","year":"2011","journal-title":"Pharmacogenom. J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1111\/jdv.17520","article-title":"Effect of baseline disease severity on achievement of treatment target with apremilast: Results from a pooled analysis","volume":"35","author":"Reich","year":"2021","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1111\/bjd.20710","article-title":"Systemic antipsoriatic treatment: Do women respond better than men and if so, why?","volume":"185","author":"Wolf","year":"2021","journal-title":"Br. J. Dermatol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e010","DOI":"10.1097\/JW9.0000000000000010","article-title":"The impact of gender and sex in psoriasis: What to be aware of when treating women with psoriasis","volume":"8","author":"Guillet","year":"2022","journal-title":"Int. J. 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