Increased Gene Copy Number of DEFA1A3 Is Associated With the Severity of Ulcerative Colitis.
Journal
Clinical and translational gastroenterology
ISSN: 2155-384X
Titre abrégé: Clin Transl Gastroenterol
Pays: United States
ID NLM: 101532142
Informations de publication
Date de publication:
06 04 2021
06 04 2021
Historique:
received:
13
11
2020
accepted:
17
02
2021
entrez:
7
4
2021
pubmed:
8
4
2021
medline:
10
9
2021
Statut:
epublish
Résumé
DEFA1A3 encodes human neutrophil peptides (HNPs) 1-3 and has multiple copy number variations (CNVs). HNPs are associated with innate immunity. Ulcerative colitis (UC), a chronic inflammatory gastrointestinal disorder, is a life-threatening condition, and predictive markers of UC severity are needed. This study investigated the relationship between DEFA1A3 CNV and UC severity. This study enrolled 165 patients with UC. The relationship between DEFA1A3 CNV and disease severity was analyzed based on Mayo score, patient characteristics, and treatment methods. In addition, serum and stimulated neutrophil-derived HNP concentrations were also measured in patients with high and low DEFA1A3 CNV. DEFA1A3 CNV was significantly correlated with Mayo score and white blood cell count (R = 0.46, P < 0.0001; R = 0.29, P = 0.003, respectively), and only high copy numbers of DEFA1A3 were independent factors for severe UC (P < 0.001, odds ratio: 1.88, 95% confidence interval, 1.34-2.61). The number of severe UC patients with high DEFA1A3 CNV was significantly greater than those with low CNV. We confirmed the associations between DEFA1A3 and UC severity using a validation cohort. In addition, the HNP concentration in high-copy number patients was significantly higher after neutrophil stimulation than that in low-copy number patients. This study demonstrated that there is a correlation between DEFA1A3 copy number and severity in patients with UC. In addition, neutrophils from UC patients with higher DEFA1A3 CNV had high reactivity of secretion of HNPs after stimulation. DEFA1A3 CNV may be a novel severity marker and a potential therapeutic target for UC.
Identifiants
pubmed: 33825720
doi: 10.14309/ctg.0000000000000331
pii: 01720094-202104000-00005
pmc: PMC8032364
doi:
Substances chimiques
DEFA1A3 protein, human
0
Peptides, Cyclic
0
alpha-Defensins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e00331Informations de copyright
Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.
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