Associations of A20, CYLD, Cezanne and JAK2 Genes and Immunophenotype with Psoriasis Susceptibility
<i>Background and Objectives</i>: 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 cylindrom...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-10-01
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| Series: | Medicina |
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| Online Access: | https://www.mdpi.com/1648-9144/59/10/1766 |
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| author | Nguyen Hoang Giang Nguyen Thi Kim Lien Do Thi Trang Pham Thi Huong Nguyen Huy Hoang Nguyen Thi Xuan |
| author_facet | Nguyen Hoang Giang Nguyen Thi Kim Lien Do Thi Trang Pham Thi Huong Nguyen Huy Hoang Nguyen Thi Xuan |
| author_sort | Nguyen Hoang Giang |
| collection | DOAJ |
| description | <i>Background and Objectives</i>: 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. <i>Materials and Methods</i>: 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). <i>Results</i>: The inactivation of A20, CYLD and Cezanne and increased levels of TNF-α, IFN-γ 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<sup>+</sup>CD117<sup>−</sup> and CD19<sup>+</sup>CD23<sup>+</sup> (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-γ than those with normal CA 125 levels. <i>Conclusions</i>: A20 expression was associated with lipid metabolism and the recruitment of CD13<sup>+</sup> CD117<sup>−</sup> 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. |
| first_indexed | 2024-03-10T21:04:49Z |
| format | Article |
| id | doaj.art-8a7c459d01b74abda70c37c6c3ff402d |
| institution | Directory Open Access Journal |
| issn | 1010-660X 1648-9144 |
| language | English |
| last_indexed | 2024-03-10T21:04:49Z |
| publishDate | 2023-10-01 |
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| series | Medicina |
| spelling | doaj.art-8a7c459d01b74abda70c37c6c3ff402d2023-11-19T17:16:54ZengMDPI AGMedicina1010-660X1648-91442023-10-015910176610.3390/medicina59101766Associations of A20, CYLD, Cezanne and JAK2 Genes and Immunophenotype with Psoriasis SusceptibilityNguyen Hoang Giang0Nguyen Thi Kim Lien1Do Thi Trang2Pham Thi Huong3Nguyen Huy Hoang4Nguyen Thi Xuan5Institute of Genome Research, Vietnam Academy of Science and Technology, Hoang Quoc Viet, Ha Noi 100000, VietnamInstitute of Genome Research, Vietnam Academy of Science and Technology, Hoang Quoc Viet, Ha Noi 100000, VietnamInstitute of Genome Research, Vietnam Academy of Science and Technology, Hoang Quoc Viet, Ha Noi 100000, VietnamInstitute of Genome Research, Vietnam Academy of Science and Technology, Hoang Quoc Viet, Ha Noi 100000, VietnamInstitute of Genome Research, Vietnam Academy of Science and Technology, Hoang Quoc Viet, Ha Noi 100000, VietnamInstitute of Genome Research, Vietnam Academy of Science and Technology, Hoang Quoc Viet, Ha Noi 100000, Vietnam<i>Background and Objectives</i>: 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. <i>Materials and Methods</i>: 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). <i>Results</i>: The inactivation of A20, CYLD and Cezanne and increased levels of TNF-α, IFN-γ 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<sup>+</sup>CD117<sup>−</sup> and CD19<sup>+</sup>CD23<sup>+</sup> (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-γ than those with normal CA 125 levels. <i>Conclusions</i>: A20 expression was associated with lipid metabolism and the recruitment of CD13<sup>+</sup> CD117<sup>−</sup> 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.https://www.mdpi.com/1648-9144/59/10/1766A20CezanneCYLDimmunophenotypeJAK2psoriasis |
| spellingShingle | Nguyen Hoang Giang Nguyen Thi Kim Lien Do Thi Trang Pham Thi Huong Nguyen Huy Hoang Nguyen Thi Xuan Associations of A20, CYLD, Cezanne and JAK2 Genes and Immunophenotype with Psoriasis Susceptibility Medicina A20 Cezanne CYLD immunophenotype JAK2 psoriasis |
| title | Associations of A20, CYLD, Cezanne and JAK2 Genes and Immunophenotype with Psoriasis Susceptibility |
| title_full | Associations of A20, CYLD, Cezanne and JAK2 Genes and Immunophenotype with Psoriasis Susceptibility |
| title_fullStr | Associations of A20, CYLD, Cezanne and JAK2 Genes and Immunophenotype with Psoriasis Susceptibility |
| title_full_unstemmed | Associations of A20, CYLD, Cezanne and JAK2 Genes and Immunophenotype with Psoriasis Susceptibility |
| title_short | Associations of A20, CYLD, Cezanne and JAK2 Genes and Immunophenotype with Psoriasis Susceptibility |
| title_sort | associations of a20 cyld cezanne and jak2 genes and immunophenotype with psoriasis susceptibility |
| topic | A20 Cezanne CYLD immunophenotype JAK2 psoriasis |
| url | https://www.mdpi.com/1648-9144/59/10/1766 |
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