Risk of chronic pancreatitis in carriers of loss-of-function CTRC variants: A meta-analysis.

Autor: Takáts A; Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary., Berke G; Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary., Gede N; Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary., Németh BC; Department of Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary., Witt H; Pediatric Nutritional Medicine & Else Kröner-Fresenius-Centre for Nutritional Medicine (EKFZ), Technical University Munich (TUM), Munich, Germany., Głuszek S; Collegium Medicum Jan Kochanowski University, Kielce, Poland., Rygiel AM; Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland., Hegyi P; Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.; Department of Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.; Centre for Translational Medicine, Semmelweis University, Budapest, Hungary., Sahin-Tóth M; Department of Surgery, University of California Los Angeles, Los Angeles, California, United States of America., Hegyi E; Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2022 May 20; Vol. 17 (5), pp. e0268859. Date of Electronic Publication: 2022 May 20 (Print Publication: 2022).
DOI: 10.1371/journal.pone.0268859
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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