TY  - JOUR
A1  -  Takáts Amanda
A1  -  Berke Gerg?
A1  -  Gede Noémi
A1  -  Németh Balázs
A1  -  Witt Heiko
A1  -  G?uszek Stanis?aw
A1  -  Rygiel Agnieszka Magdalena
A1  -  Hegyi Péter
A1  -  Sahin-Tóth Miklós
A1  -  Hegyi Eszter
N2  - 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.
SP  - Terjedelem: 14 p.
TI  - Risk of chronic pancreatitis in carriers of loss-of-function CTRC variants: A meta-analysis
UR  - http://doi.org/10.1371/journal.pone.0268859
ID  - publicatio24658
Y1  - 2022///
AV  - public
N1  - Megosztott els? szerz?ség
IS  - 5
EP  - Azonosító: e0268859
JF  - PLOS ONE
SN  - 1932-6203
VL  - 17
ER  -