Extensive molecular analysis suggested the strong genetic heterogeneity of idiopathic chronic pancreatitis

Valentina Maria Sofia, Letizia Da Sacco, Cecilia Surace, Anna Cristina Tomaiuolo, Silvia Genovese, Simona Grotta, Maria Gnazzo, Stefano Petrocchi, Laura Ciocca, Federico Alghisi, Enza Montemitro, Luigi Martemucci, Ausilia Elce, Vincenzina Lucidi, Giuseppe Castaldo, Adriano Angioni

Research output: Contribution to journalArticlepeer-review


Genetic features of chronic pancreatitis (CP) have been investigated extensively, mainly by testing genes associated to the trypsinogen activation pathway. However, different molecular pathways involving other genes may be implicated in CP pathogenesis. A total of 80 patients with idiopathic chronic pancreatitis (ICP) were investigated using a Next-Generation Sequencing (NGS) approach with a panel of 70 genes related to six different pancreatic pathways: premature activation of trypsinogen, modifier genes of cystic fibrosis phenotype, pancreatic secretion and ion homeostasis, calcium signaling and zymogen granules (ZG) exocytosis, autophagy and autoimmune pancreatitis-related genes. We detected mutations in 34 out of 70 genes examined; of the 80 patients, 64 (80.0%) were positive for mutations in one or more genes and 16 (20.0%) had no mutations. Mutations in CFTR were detected in 32 of the 80 patients (40.0%) and 22 of them exhibited at least one mutation in genes of other pancreatic pathways. Of the remaining 48 patients, 13/80 (16.3%) had mutations in genes involved in premature activation of trypsinogen and 19/80 (23.8%) had mutations only in genes of the other pathways: 38 (59.3%) of the 64 patients positive for mutations showed variants in two or more genes. Our data, although to be extended with functional analysis of novel mutations, suggest a high rate of genetic heterogeneity in CP and that trans-heterozygosity may predispose to the ICP phenotype.

Original languageEnglish
Pages (from-to)300-309
Number of pages10
JournalMolecular Medicine
Publication statusPublished - 2016

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'Extensive molecular analysis suggested the strong genetic heterogeneity of idiopathic chronic pancreatitis'. Together they form a unique fingerprint.

Cite this