Protease-Sensitive Pancreatic Lipase Variants Are Associated With Early Onset Chronic Pancreatitis

The American Journal of Gastroenterology
Denise LasherMiklós Sahin-Tóth

Abstract

Premature activation of the digestive protease trypsin within the pancreatic parenchyma is a critical factor in the pathogenesis of pancreatitis. Alterations in genes that affect intrapancreatic trypsin activity are associated with chronic pancreatitis (CP). Recently, carboxyl ester lipase emerged as a trypsin-independent risk gene. Here, we evaluated pancreatic lipase (PNLIP) as a potential novel susceptibility gene for CP. We analyzed all 13 PNLIP exons in 429 nonalcoholic patients with CP and 600 control subjects from Germany, in 632 patients and 957 controls from France, and in 223 patients and 1,070 controls from Japan by DNA sequencing. Additionally, we analyzed selected exons in further 545 patients with CP and 1,849 controls originating from Germany, United States, and India. We assessed the cellular secretion, lipase activity, and proteolytic stability of recombinant PNLIP variants. In the German discovery cohort, 8/429 (1.9%) patients and 2/600 (0.3%) controls carried a PNLIP missense variant (P = 0.02, odds ratio [OR] = 5.7, 95% confidence interval [CI] = 1.1-38.9). Variants detected in patients were prone to proteolytic degradation by trypsin and chymotrypsin. In the French replication cohort, protease-sensitive var...Continue Reading

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Citations

May 15, 2019·The American Journal of Gastroenterology·Mahya Faghih, Vikesh K Singh
Feb 6, 2020·The Journal of Biological Chemistry·Vanda ToldiMiklós Sahin-Tóth
Jul 4, 2020·Current Opinion in Gastroenterology·Frank U WeissMarkus M Lerch
Nov 5, 2019·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Ly VilloAivar Lookene
Jan 13, 2021·Journal of Clinical Medicine·Frank U WeissMarkus M Lerch
Jan 31, 2021·The Journal of Biological Chemistry·András SzabóMiklós Sahin-Tóth
Oct 21, 2020·European Journal of Gastroenterology & Hepatology·Erling TjoraKarianne Fjeld
Aug 11, 2021·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Vanda ToldiAndrás Szabó
Sep 16, 2021·Der Internist·Jonas Rosendahl, Heiko Witt

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