Institute of Genome Research, Vietnam Academy of Science and Technology, Hoang Quoc Viet, Ha Noi 100000, Vietnam.
Department of Biotechnology, University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, Hoang Quoc Viet, Ha Noi 100000, Vietnam.
Medicina (Kaunas). 2023 Oct 3;59(10):1766. doi: 10.3390/medicina59101766.
: 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. : 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). : 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 CD13CD117 and CD19CD23 (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. : A20 expression was associated with lipid metabolism and the recruitment of CD13 CD117 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.
银屑病是一种免疫介导的慢性炎症性皮肤疾病，通常伴有明显的红斑、增厚和鳞屑。去泛素化酶基因，如肿瘤坏死因子-α 蛋白 3（TNFAIP3，A20）、圆柱瘤病（CYLD）和 Cezanne，通过 Janus 激酶/信号转导和转录激活因子（JAK-STAT）途径作为炎症反应的负调节剂。在这项研究中，测定了银屑病患者 A20、CYLD 和 Cezanne 基因的多态性和表达以及免疫表型。
共纳入 82 例银屑病患者和 147 例临床特征明确的健康个体。通过直接 DNA 测序确定基因多态性，通过定量实时聚合酶链反应（PCR）确定基因表达谱，通过流式细胞术确定免疫表型，通过酶联免疫吸附试验（ELISA）确定细胞因子和癌抗原（CA）125 的分泌。
在银屑病患者中观察到 A20、CYLD 和 Cezanne 的失活以及 TNF-α、IFN-γ 和 CA 125 水平的升高。重要的是，A20 表达水平低的患者甘油三酯和总胆固醇浓度显著升高，CD13CD117 和 CD19CD23（激活 B）细胞数量也高于 A20 表达水平高的患者。遗传分析表明，JAK2 基因中的所有 rs4495487 单核苷酸多态性、A20 基因中的 rs200878487 单核苷酸多态性以及 Cezanne 基因中的四个单核苷酸多态性（c.1584-375、c.1584-374、rs1230581026 和 p.W433R）均与显著风险相关，而 JAK2 基因中的 rs10974947 变体则降低了银屑病的风险。此外，在 Cezanne 基因中，Polyphen-2 预测工具预测 p.W433R 可能具有损害性，AA/CC 单倍型与银屑病的高风险相关。此外，CA 125 水平高于临床截断值 35 U/mL 的患者 IFN-γ 水平高于 CA 125 水平正常的患者。
A20 表达与银屑病患者的脂质代谢和 CD13 CD117 和激活 B 细胞募集到循环中有关。此外，Cezanne 基因中 p.W433R 变体的有害影响可能导致银屑病的风险增加。
