PMID- 37893484
OWN - NLM
STAT- MEDLINE
DCOM- 20231030
LR  - 20231031
IS  - 1648-9144 (Electronic)
IS  - 1010-660X (Print)
IS  - 1010-660X (Linking)
VI  - 59
IP  - 10
DP  - 2023 Oct 3
TI  - Associations of A20, CYLD, Cezanne and JAK2 Genes and Immunophenotype with 
      Psoriasis Susceptibility.
LID - 10.3390/medicina59101766 [doi]
LID - 1766
AB  - 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-alpha, IFN-gamma 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(-) 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-gamma than those with 
      normal CA 125 levels. Conclusions: 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.
FAU - Giang, Nguyen Hoang
AU  - Giang NH
AD  - Institute of Genome Research, Vietnam Academy of Science and Technology, Hoang 
      Quoc Viet, Ha Noi 100000, Vietnam.
FAU - Lien, Nguyen Thi Kim
AU  - Lien NTK
AD  - Institute of Genome Research, Vietnam Academy of Science and Technology, Hoang 
      Quoc Viet, Ha Noi 100000, Vietnam.
FAU - Trang, Do Thi
AU  - Trang DT
AD  - Institute of Genome Research, Vietnam Academy of Science and Technology, Hoang 
      Quoc Viet, Ha Noi 100000, Vietnam.
FAU - Huong, Pham Thi
AU  - Huong PT
AD  - Institute of Genome Research, Vietnam Academy of Science and Technology, Hoang 
      Quoc Viet, Ha Noi 100000, Vietnam.
FAU - Hoang, Nguyen Huy
AU  - Hoang NH
AUID- ORCID: 0000-0002-6284-5813
AD  - Institute of Genome Research, Vietnam Academy of Science and Technology, Hoang 
      Quoc Viet, Ha Noi 100000, Vietnam.
AD  - Department of Biotechnology, University of Science and Technology of Hanoi, 
      Vietnam Academy of Science and Technology, Hoang Quoc Viet, Ha Noi 100000, 
      Vietnam.
FAU - Xuan, Nguyen Thi
AU  - Xuan NT
AUID- ORCID: 0000-0003-3494-5136
AD  - Institute of Genome Research, Vietnam Academy of Science and Technology, Hoang 
      Quoc Viet, Ha Noi 100000, Vietnam.
AD  - Department of Biotechnology, University of Science and Technology of Hanoi, 
      Vietnam Academy of Science and Technology, Hoang Quoc Viet, Ha Noi 100000, 
      Vietnam.
LA  - eng
GR  - VAST02.05/21-22/Vietnam Academy of Science and Technology/
PT  - Journal Article
DEP - 20231003
PL  - Switzerland
TA  - Medicina (Kaunas)
JT  - Medicina (Kaunas, Lithuania)
JID - 9425208
RN  - 0 (Cytokines)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.10.2 (JAK2 protein, human)
RN  - EC 2.7.10.2 (Janus Kinase 2)
RN  - EC 3.4.19.12 (CYLD protein, human)
RN  - EC 3.4.19.12 (Deubiquitinating Enzyme CYLD)
SB  - IM
MH  - Humans
MH  - *Signal Transduction
MH  - Cytokines/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - *Psoriasis/genetics
MH  - Janus Kinase 2/genetics/metabolism
MH  - Deubiquitinating Enzyme CYLD/metabolism
PMC - PMC10608350
OTO - NOTNLM
OT  - A20
OT  - CYLD
OT  - Cezanne
OT  - JAK2
OT  - immunophenotype
OT  - psoriasis
COIS- The authors declare no conflict of interest.
EDAT- 2023/10/28 11:44
MHDA- 2023/10/30 06:46
PMCR- 2023/10/03
CRDT- 2023/10/28 01:10
PHST- 2023/06/29 00:00 [received]
PHST- 2023/08/14 00:00 [revised]
PHST- 2023/08/31 00:00 [accepted]
PHST- 2023/10/30 06:46 [medline]
PHST- 2023/10/28 11:44 [pubmed]
PHST- 2023/10/28 01:10 [entrez]
PHST- 2023/10/03 00:00 [pmc-release]
AID - medicina59101766 [pii]
AID - medicina-59-01766 [pii]
AID - 10.3390/medicina59101766 [doi]
PST - epublish
SO  - Medicina (Kaunas). 2023 Oct 3;59(10):1766. doi: 10.3390/medicina59101766.