Risk of chronic pancreatitis in carriers of the c.180C>T (p.Gly60=) CTRC variant: case-control studies and meta-analysis.

Autor: Berke G; Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary., Beer S; Division of Gastroenterology, Medical Department II, University of Leipzig Medical Center, Leipzig, Germany., Gede N; Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary., Takáts A; Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary., Szentesi A; Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary., Hegyi P; Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary; Centre for Translational Medicine, Semmelweis University, Budapest, Hungary; Division of Pancreatic Diseases, Heart and Vascular Centre, Semmelweis University, Budapest, Hungary., Rosendahl J; Department of Internal Medicine I, Martin Luther University, Halle (Saale), Germany., Sahin-Tóth M; Department of Surgery, University of California Los Angeles, Los Angeles, CA, USA., Németh BC; Department of Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary; Hungarian Centre of Excellence for Molecular Medicine, University of Szeged, Translational Pancreatology Research Group, Szeged, Hungary., Hegyi E; Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary. Electronic address: eszter.hegyi@aok.pte.hu.
Jazyk: angličtina
Zdroj: Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] [Pancreatology] 2023 Aug; Vol. 23 (5), pp. 481-490. Date of Electronic Publication: 2023 May 29.
DOI: 10.1016/j.pan.2023.05.013
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors have declared that no conflict of interest exists.
(Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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