Pathogenetics of Chronic Pancreatitis

  • Zhuan Liao
  • Zhao-Shen Li
  • David N. Cooper
  • Claude Férec
  • Jian-Min Chen


Chronic pancreatitis is a condition that is associated with the progressive inflammation of the pancreas which over time gives rise to irreversible morphological changes accompanied by impairment of both exocrine and endocrine functions (Majumder and Chari 2016). Over the last 20 years, molecular genetics has played an increasingly important role in elucidating the aetiology of chronic pancreatitis. The dawn of the new era in the genetic analysis of autosomal dominant hereditary pancreatitis (OMIM #167800) was heralded by the mapping of a disease locus to the long arm of chromosome 7 (Le Bodic et al. 1996; Pandya et al. 1996; Whitcomb et al. 1996b) and the subsequent identification of a gain-of-function missense mutation (i.e., p.Arg122His) in the cationic trypsinogen gene (PRSS1; OMIM #276000) (Whitcomb et al. 1996a). Thereafter, a steady stream of chronic pancreatitis susceptibility (or protective) variants in different genes has been reported. The analysis of variants in four specific genes, all highly expressed in human pancreatic acinar cells [PRSS1, PRSS2 (encoding anionic trypsinogen; OMIM #601564), SPINK1 (encoding pancreatic secretory trypsin inhibitor; OMIM #167790) and CTRC (encoding chymotrypsin C, which specifically degrades all human trypsinogen/trypsin isoforms (OMIM #601405) (Szmola and Sahin-Tóth 2007))] has firmly established the importance of a homeostatic balance between the activation and inactivation of trypsinogen within the pancreas, thereby defining a trypsin-dependent pathway in the pathogenesis of chronic pancreatitis. Whereas gain-of-function missense mutations and copy number variants in PRSS1 (Le Maréchal et al. 2006; Whitcomb et al. 1996a) and loss-of-function variants in SPINK1 (Witt et al. 2000) and CTRC (Masson et al. 2008b; Rosendahl et al. 2008) predispose to chronic pancreatitis, loss-of-function variants in PRSS1 (Boulling et al. 2015; Chen et al. 2003; Derikx et al. 2015; Whitcomb et al. 2012) and PRSS2 (Witt et al. 2006) protect against the disease.


Chronic pancreatitis Genetics Human pancreatic acinar cells Pathogenesis Susceptibility genes 



Carboxyl ester lipase


Cystic fibrosis transmembrane conductance regulator




Carboxypeptidase A1


Chymotrypsin C


Endoplasmic reticulum stress


Fucosyltransferase 2


Genome-wide association study


Idiopathic chronic pancreatitis


Maturity-onset diabetes of the young


Nonalcoholic chronic pancreatitis


Non-allelic homologous recombination


Nonsense-mediated mRNA decay


Odds ratio


Polymerase chain reaction


Recurrent acute pancreatitis


Reverse transcription polymerase chain reaction


Single nucleotide polymorphism


Variable number tandem repeat



The work was supported by the Conseil Régional de Bretagne, the Association des Pancréatites Chroniques Héréditaires, the Association de Transfusion Sanguine et de Biogénétique Gaetan Saleun, and the Institut National de la Santé et de la Recherche Médicale (INSERM), France; and the National Natural Science Foundation of China (81470884 and 81422010 to ZL), the Shuguang Program of Shanghai Education Development Foundation and Shanghai Municipal Education Commission (15SG33 to ZL) and the Chang Jiang Scholars Program of Ministry of Education (Q2015190 to ZL), China.


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Copyright information

© Springer Nature Singapore Pte Ltd. and Shanghai Scientific and Technical Publishers 2017

Authors and Affiliations

  • Zhuan Liao
    • 1
    • 2
  • Zhao-Shen Li
    • 1
    • 2
  • David N. Cooper
    • 3
  • Claude Férec
    • 4
    • 5
    • 6
    • 7
  • Jian-Min Chen
    • 4
    • 5
    • 6
  1. 1.Department of GastroenterologyChanghai Hospital, the Second Military Medical UniversityShanghaiChina
  2. 2.Shanghai Institute of Pancreatic DiseasesShanghaiChina
  3. 3.Institute of Medical Genetics, School of MedicineCardiff UniversityCardiffUK
  4. 4.Institut National de la Santé et de la Recherche Médicale (INSERM)BrestFrance
  5. 5.Faculté de Médecine et des Sciences de la SantéUniversité de Bretagne Occidentale (UBO)BrestFrance
  6. 6.Etablissement Français du Sang (EFS)—BretagneBrestFrance
  7. 7.Laboratoire de Génétique Moléculaire et d’HistocompatibilitéCentre Hospitalier Universitaire (CHU) Brest, Hôpital MorvanBrestFrance

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