{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T12:58:56Z","timestamp":1788785936942,"version":"build-2803163510"},"reference-count":42,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T00:00:00Z","timestamp":1696291200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012046","name":"Vietnam Academy of Science and Technology","doi-asserted-by":"publisher","award":["VAST02.05\/21-22"],"award-info":[{"award-number":["VAST02.05\/21-22"]}],"id":[{"id":"10.13039\/100012046","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Psoriasis is an immune-mediated chronic inflammatory skin disorder and commonly associated with highly noticeable erythematous, thickened and scaly plaques. Deubiquitinase genes, such as tumor necrosis factor-alpha protein 3 (TNFAIP3, A20), the cylindromatosis (CYLD) and Cezanne, function as negative regulators of inflammatory response through the Janus kinase\/signal transducers and activators of transcription (JAK-STAT) pathways. In this study, polymorphisms and expressions of A20, CYLD and Cezanne genes as well as immunophenotype in psoriatic patients were determined. Materials and Methods: In total, 82 patients with psoriasis and 147 healthy individuals with well-characterized clinical profiles were enrolled. Gene polymorphisms were determined by direct DNA sequencing, gene expression profile by quantitative real time-polymerase chain reaction (PCR), immunophenotype by flow cytometry, and the secretion of cytokines and cancer antigen (CA) 125 by enzyme-linked Immunosorbent assay (ELISA). Results: The inactivation of A20, CYLD and Cezanne and increased levels of TNF-\u03b1, IFN-\u03b3 and CA 125 was observed in psoriatic patients. Importantly, patients with low A20 expression had significant elevations of triglyceride and total cholesterol concentrations and higher numbers of CD13+CD117\u2212 and CD19+CD23+ (activated B) cells than those with high A20 expression. Genetic analysis indicated that all rs4495487 SNPs in the JAK2 gene, rs200878487 SNPs in the A20 gene and four SNPs (c.1584-375, c.1584-374, rs1230581026 and p.W433R) in the Cezanne gene were associated with significant risks, while the rs10974947 variant in the JAK2 gene was at reduced risk of psoriasis. Moreover, in the Cezanne gene, p.W433R was predicted to be probably damaging by the Polyphen-2 prediction tool and an AA\/CC haplotype was associated with a high risk of psoriasis. In addition, patients with higher CA 125 levels than the clinical cutoff 35 U\/mL showed increased levels of IFN-\u03b3 than those with normal CA 125 levels. Conclusions: A20 expression was associated with lipid metabolism and the recruitment of CD13+ CD117\u2212 and activated B cells into circulation in psoriatic patients. Besides this, the deleterious effect of the p.W433R variant in the Cezanne gene may contribute to the risk of psoriasis.<\/jats:p>","DOI":"10.3390\/medicina59101766","type":"journal-article","created":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T07:47:52Z","timestamp":1696405672000},"page":"1766","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Associations of A20, CYLD, Cezanne and JAK2 Genes and Immunophenotype with Psoriasis Susceptibility"],"prefix":"10.3390","volume":"59","author":[{"given":"Nguyen Hoang","family":"Giang","sequence":"first","affiliation":[{"name":"Institute of Genome Research, Vietnam Academy of Science and Technology, Hoang Quoc Viet, Ha Noi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Thi Kim","family":"Lien","sequence":"additional","affiliation":[{"name":"Institute of Genome Research, Vietnam Academy of Science and Technology, Hoang Quoc Viet, Ha Noi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Do Thi","family":"Trang","sequence":"additional","affiliation":[{"name":"Institute of Genome Research, Vietnam Academy of Science and Technology, Hoang Quoc Viet, Ha Noi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pham Thi","family":"Huong","sequence":"additional","affiliation":[{"name":"Institute of Genome Research, Vietnam Academy of Science and Technology, Hoang Quoc Viet, Ha Noi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6284-5813","authenticated-orcid":false,"given":"Nguyen Huy","family":"Hoang","sequence":"additional","affiliation":[{"name":"Institute of Genome Research, Vietnam Academy of Science and Technology, Hoang Quoc Viet, Ha Noi 100000, Vietnam"},{"name":"Department of Biotechnology, University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, Hoang Quoc Viet, Ha Noi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3494-5136","authenticated-orcid":false,"given":"Nguyen Thi","family":"Xuan","sequence":"additional","affiliation":[{"name":"Institute of Genome Research, Vietnam Academy of Science and Technology, Hoang Quoc Viet, Ha Noi 100000, Vietnam"},{"name":"Department of Biotechnology, University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, Hoang Quoc Viet, Ha Noi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jaut.2015.08.015","article-title":"The genetics of human autoimmune disease: A perspective on progress in the field and future directions","volume":"64","author":"Seldin","year":"2015","journal-title":"J. Autoimmun."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.1016\/j.jid.2016.04.032","article-title":"The Spectrum of Mild to Severe Psoriasis Vulgaris Is Defined by a Common Activation of IL-17 Pathway Genes, but with Key Differences in Immune Regulatory Genes","volume":"136","author":"Kim","year":"2016","journal-title":"J. Investig. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1038\/sj.jid.5701213","article-title":"Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells","volume":"128","author":"Lowes","year":"2008","journal-title":"J. Investig. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e5374","DOI":"10.1590\/1414-431x20165374","article-title":"CD19+ B cell subsets in the peripheral blood and skin lesions of psoriasis patients and their correlations with disease severity","volume":"49","author":"Lu","year":"2016","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1159\/000328011","article-title":"Natural killer cells in psoriasis","volume":"3","author":"Tobin","year":"2011","journal-title":"J. Innate. Immun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7553","DOI":"10.1038\/s41598-017-07975-2","article-title":"Signs of innate immune activation and premature immunosenescence in psoriasis patients","volume":"7","author":"Sahmatova","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1006\/jaut.1999.0343","article-title":"CD69, HLA-DR and the IL-2R identify persistently activated T cells in psoriasis vulgaris lesional skin: Blood and skin comparisons by flow cytometry","volume":"14","author":"Ferenczi","year":"2000","journal-title":"J. Autoimmun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jdermsci.2015.11.003","article-title":"IL-10-producing regulatory B cells are decreased in patients with psoriasis","volume":"81","author":"Hayashi","year":"2016","journal-title":"J. Dermatol. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1007\/s40265-017-0701-9","article-title":"JAK-STAT Signaling as a Target for Inflammatory and Autoimmune Diseases: Current and Future Prospects","volume":"77","author":"Banerjee","year":"2017","journal-title":"Drugs"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1002\/jcp.25941","article-title":"APN\/CD13 is over-expressed by Psoriatic fibroblasts and is modulated by CGRP and IL-4 but not by retinoic acid treatment","volume":"233","author":"Gerbaud","year":"2018","journal-title":"J. Cell Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/0923-1811(91)90022-P","article-title":"Mononuclear cell-bound CD23 is elevated in both atopic dermatitis and psoriasis","volume":"2","author":"Muller","year":"1991","journal-title":"J. Dermatol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4049\/jimmunol.1900868","article-title":"CD13\/Aminopeptidase N Is a Potential Therapeutic Target for Inflammatory Disorders","volume":"204","author":"Lu","year":"2020","journal-title":"J. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s11033-017-4122-3","article-title":"Dishevelled proteins and CYLD reciprocally regulate each other in CML cell lines","volume":"44","author":"Caliskan","year":"2017","journal-title":"Mol. Biol. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4918","DOI":"10.1182\/blood-2008-08-174110","article-title":"The NF-kappaB negative regulator TNFAIP3 (A20) is inactivated by somatic mutations and genomic deletions in marginal zone lymphomas","volume":"113","author":"Novak","year":"2009","journal-title":"Blood"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/1475-2867-14-36","article-title":"Abnormal expression of A20 and its regulated genes in peripheral blood from patients with lymphomas","volume":"14","author":"Wang","year":"2014","journal-title":"Cancer Cell Int."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s12967-015-0396-1","article-title":"Decreased Cezanne expression is associated with the progression and poor prognosis in hepatocellular carcinoma","volume":"13","author":"Wang","year":"2015","journal-title":"J. Transl. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.jdermsci.2020.09.005","article-title":"Associations of TNFAIP3 variants with susceptibility to psoriasis vulgaris and psoriasis arthritis in a Japanese population","volume":"100","author":"Momose","year":"2020","journal-title":"J. Dermatol. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1128\/CVI.00500-12","article-title":"Expression of tumor necrosis factor alpha-induced protein 3 mRNA in peripheral blood mononuclear cells negatively correlates with disease severity in psoriasis vulgaris","volume":"19","author":"Jiang","year":"2012","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.3892\/ijmm.2016.2514","article-title":"The inhibitory effect of A20 on the inflammatory reaction of epidermal keratinocytes","volume":"37","author":"Sohn","year":"2016","journal-title":"Int. J. Mol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2637","DOI":"10.1038\/jid.2009.157","article-title":"An association study of 22 candidate genes in psoriasis families reveals shared genetic factors with other autoimmune and skin disorders","volume":"129","author":"Oudot","year":"2009","journal-title":"J. Investig. Dermatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1111\/cei.12888","article-title":"A preliminary study of new single polymorphisms in the T helper type 17 pathway for psoriasis in the Korean population","volume":"187","author":"Kim","year":"2017","journal-title":"Clin. Exp. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1007\/s12640-021-00456-5","article-title":"VSIG4 Attenuates NLRP3 and Ameliorates Neuroinflammation via JAK2-STAT3-A20 Pathway after Intracerebral Hemorrhage in Mice","volume":"40","author":"Ji","year":"2022","journal-title":"Neurotox. Res."},{"key":"ref_23","unstructured":"W.H.O. (2023, May 12). Global Report on Psoriasis. Available online: https:\/\/www.who.int\/publications\/i\/item\/9789241565189."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_25","first-page":"204","article-title":"Association of two variants of the interferon-alpha receptor-1 gene with the presentation of hepatitis B virus infection","volume":"19","author":"Xuan","year":"2008","journal-title":"Eur. Cytokine Netw."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1080\/10799893.2020.1808678","article-title":"Regulation of cell activation by A20 through STAT signaling in acute lymphoblastic leukemia","volume":"41","author":"Canh","year":"2021","journal-title":"J. Recept. Signal Transduct. Res."},{"key":"ref_27","first-page":"93","article-title":"Serum CA125 elevation is independently associated with serositis in SLE patients","volume":"30","author":"Yang","year":"2012","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1196\/annals.1422.037","article-title":"Increased production of the soluble tumor-associated antigens CA19-9, CA125, and CA15-3 in rheumatoid arthritis: Potential adhesion molecules in synovial inflammation?","volume":"1108","author":"Szekanecz","year":"2007","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1038\/s41590-020-0634-4","article-title":"Non-catalytic ubiquitin binding by A20 prevents psoriatic arthritis-like disease and inflammation","volume":"21","author":"Razani","year":"2020","journal-title":"Nat. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/gene.2014.75","article-title":"Meta-analysis of the TNFAIP3 region in psoriasis reveals a risk haplotype that is distinct from other autoimmune diseases","volume":"16","author":"Nititham","year":"2015","journal-title":"Genes Immun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/ng.3459","article-title":"Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease","volume":"48","author":"Zhou","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Aki, A., Nagasaki, M., Malynn, B.A., Ma, A., and Kagari, T. (2017). Hypomorphic A20 expression confers susceptibility to psoriasis. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0180481"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"369","DOI":"10.17219\/acem\/144027","article-title":"Prevalence of CYLD mutations in Vietnamese patients with polycythemia vera","volume":"31","author":"Trang","year":"2022","journal-title":"Adv. Clin. Exp. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.cell.2006.03.041","article-title":"Cyld inhibits tumor cell proliferation by blocking Bcl-3-dependent NF-kappaB signaling","volume":"125","author":"Massoumi","year":"2006","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Ohyashiki, J.H., Yoneta, M., Hisatomi, H., Iwabuchi, T., Umezu, T., and Ohyashiki, K. (2012). The C allele of JAK2 rs4495487 is an additional candidate locus that contributes to myeloproliferative neoplasm predisposition in the Japanese population. BMC Med. Genet., 13.","DOI":"10.1186\/1471-2350-13-6"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1182\/blood-2007-06-095703","article-title":"Host genetic variation contributes to phenotypic diversity in myeloproliferative disorders","volume":"111","author":"Pardanani","year":"2008","journal-title":"Blood"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1111\/imm.12279","article-title":"Molecular mechanisms regulating CD13-mediated adhesion","volume":"142","author":"Ghosh","year":"2014","journal-title":"Immunology"},{"key":"ref_38","first-page":"e4203","article-title":"Atherogenesis in Psoriasis: Evaluation of the Serum Activities of Non-high-density Lipoprotein Cholesterol and Other Lipids Among Newly Diagnosed Psoriasis Patients","volume":"11","author":"Thungaturthi","year":"2019","journal-title":"Cureus"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Damrauer, S.M., Studer, P., da Silva, C.G., Longo, C.R., Ramsey, H.E., Csizmadia, E., Shrikhande, G.V., Scali, S.T., Libermann, T.A., and Bhasin, M.K. (2011). A20 modulates lipid metabolism and energy production to promote liver regeneration. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017715"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nm.4461","article-title":"The deubiquitinating enzyme cylindromatosis mitigates nonalcoholic steatohepatitis","volume":"24","author":"Ji","year":"2018","journal-title":"Nat. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1136\/jmg.2008.065029","article-title":"Characterisation of psoriasis susceptibility locus 6 (PSORS6) in patients with early onset psoriasis and evidence for interaction with PSORS1","volume":"46","author":"Huffmeier","year":"2009","journal-title":"J. Med. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Gonzalez, G., Lakatos, K., Hoballah, J., Fritz-Klaus, R., Al-Johani, L., Brooker, J., Jeong, S., Evans, C.L., Krauledat, P., and Cramer, D.W. (2021). Characterization of Cell-Bound CA125 on Immune Cell Subtypes of Ovarian Cancer Patients Using a Novel Imaging Platform. Cancers, 13.","DOI":"10.3390\/cancers13092072"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/10\/1766\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:04:50Z","timestamp":1760130290000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/10\/1766"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,3]]},"references-count":42,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["medicina59101766"],"URL":"https:\/\/doi.org\/10.3390\/medicina59101766","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,3]]}}}