Risk of chronic pancreatitis in carriers of the c.180C>T (p.Gly60=) CTRC variant: case-control studies and meta-analysis.
Chymotrypsin
Genetic association study
Meta-Analysis
Pancreatitis
Journal
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]
ISSN: 1424-3911
Titre abrégé: Pancreatology
Pays: Switzerland
ID NLM: 100966936
Informations de publication
Date de publication:
Aug 2023
Aug 2023
Historique:
received:
23
12
2022
revised:
06
05
2023
accepted:
28
05
2023
pmc-release:
01
08
2024
medline:
23
10
2023
pubmed:
16
6
2023
entrez:
15
6
2023
Statut:
ppublish
Résumé
Chymotrypsin C (CTRC) is a digestive serine protease produced by the pancreas that regulates intrapancreatic trypsin activity and provides a defensive mechanism against chronic pancreatitis (CP). CTRC exerts its protective effect by promoting degradation of trypsinogen, the precursor to trypsin. Loss-of-function missense and microdeletion variants of CTRC are found in around 4% of CP cases and increase disease risk by approximately 3-7-fold. In addition, a commonly occurring synonymous CTRC variant c.180C>T (p.Gly60=) was reported to increase CP risk in various cohorts but a global analysis of its impact has been lacking. Here, we analyzed the frequency and effect size of variant c.180C>T in Hungarian and pan-European cohorts, and performed meta-analysis of the new and published genetic association data. When allele frequency was considered, meta-analysis revealed an overall frequency of 14.2% in patients and 8.7% in controls (allelic odds ratio (OR) 2.18, 95% confidence interval (CI) 1.72-2.75). When genotypes were examined, c.180TT homozygosity was observed in 3.9% of CP patients and in 1.2% of controls, and c.180CT heterozygosity was present in 22.9% of CP patients and in 15.5% of controls. Relative to the c.180CC genotype, the genotypic OR values were 5.29 (95% CI 2.63-10.64), and 1.94 (95% CI 1.57-2.38), respectively, indicating stronger CP risk in homozygous carriers. Finally, we obtained preliminary evidence that the variant is associated with reduced CTRC mRNA levels in the pancreas. Taken together, the results indicate that CTRC variant c.180C>T is a clinically relevant risk factor, and should be considered when genetic etiology of CP is investigated.
Identifiants
pubmed: 37321941
pii: S1424-3903(23)00175-8
doi: 10.1016/j.pan.2023.05.013
pmc: PMC10586708
mid: NIHMS1928178
pii:
doi:
Substances chimiques
chymotrypsin C
EC 3.4.21.2
Trypsin
EC 3.4.21.4
Chymotrypsin
EC 3.4.21.1
Types de publication
Meta-Analysis
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
481-490Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK082412
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK117809
Pays : United States
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors have declared that no conflict of interest exists.
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