relation: http://publicatio.bibl.u-szeged.hu/24658/
title: Risk of chronic pancreatitis in carriers of loss-of-function CTRC variants: A meta-analysis
creator:  Takáts Amanda
creator:  Berke Gergő
creator:  Gede Noémi
creator:  Németh Balázs
creator:  Witt Heiko
creator:  Głuszek Stanisław
creator:  Rygiel Agnieszka Magdalena
creator:  Hegyi Péter
creator:  Sahin-Tóth Miklós
creator:  Hegyi Eszter
subject: 01.06. Biológiai tudományok
description: The digestive protease chymotrypsin C (CTRC) protects the pancreas against pancreatitis by degrading potentially harmful trypsinogen. Loss-of-function genetic variants in CTRC increase risk for chronic pancreatitis (CP) with variable effect size, as judged by the reported odds ratio (OR) values. Here, we performed a meta-analysis of published studies on four variants that alter the CTRC amino-acid sequence, are clinically relatively common (global carrier frequency in CP >1%), reproducibly showed association with CP and their loss of function phenotype was verified experimentally. We found strong enrichment of CTRC variants p.A73T, p.V235I, p.K247_R254del, and p.R245W in CP cases versus controls, yielding OR values of 6.5 (95% confidence interval (CI) 2.4-17.8), 4.5 (CI 2.2-9.1), 5.4 (CI 2.6-11.0), and 2.6 (CI 1.6-4.2), respectively. Subgroup analysis demonstrated disease association of variants p.K247_R254del and p.R245W in alcoholic CP with similar effect sizes as seen in the overall CP group. Homozygosity or compound heterozygosity were rare and seemed to be associated with higher risk. We also identified a so far unreported linkage disequilibrium between variant p.K247_R254del and the common c.180C>T (p.G60 =) haplotype. Taken together, the results indicate that heterozygous loss-of-function CTRC variants increase the risk for CP approximately 3-7-fold. This meta-analysis confirms the clinical significance of CTRC variants and provides further justification for the genetic screening of CP patients.
date: 2022
type: Folyóiratcikk
type: PeerReviewed
format: text
identifier: http://publicatio.bibl.u-szeged.hu/24658/1/Takats2022.pdf
identifier:     Takáts Amanda;  Berke Gergő;  Gede Noémi;  Németh Balázs;  Witt Heiko;  Głuszek Stanisław;  Rygiel Agnieszka Magdalena;  Hegyi Péter;  Sahin-Tóth Miklós;  Hegyi Eszter: Risk of chronic pancreatitis in carriers of loss-of-function CTRC variants: A meta-analysis.   PLOS ONE, 17 (5).  Terjedelem: 14 p.-Azonosító: e0268859.  ISSN 1932-6203 (2022)     
identifier: doi:10.1371/journal.pone.0268859
relation: http://doi.org/10.1371/journal.pone.0268859
relation: 32837109
language: eng