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. 2018 Jul 27;24(1):38.
doi: 10.1186/s10020-018-0041-6.

Trans-heterozygosity for mutations enhances the risk of recurrent/chronic pancreatitis in patients with Cystic Fibrosis

Valentina Maria Sofia  1 , Cecilia Surace  1 , Vito Terlizzi  2 , Letizia Da Sacco  3 , Federico Alghisi  4 , Antonella Angiolillo  5 , Cesare Braggion  2 , Natalia Cirilli  6 , Carla Colombo  7 , Antonella Di Lullo  8   9 , Rita Padoan  10 , Serena Quattrucci  11 , Valeria Raia  12 , Giuseppe Tuccio  13 , Federica Zarrilli  14 , Anna Cristina Tomaiuolo  1 , Antonio Novelli  1 , Vincenzina Lucidi  4 , Marco Lucarelli  15   16 , Giuseppe Castaldo  8   17 , Adriano Angioni  18
Affiliations

Trans-heterozygosity for mutations enhances the risk of recurrent/chronic pancreatitis in patients with Cystic Fibrosis

Valentina Maria Sofia et al. Mol Med. .

Abstract

Background: Recurrent (RP) and chronic pancreatitis (CP) may complicate Cystic Fibrosis (CF). It is still unknown if mutations in genes involved in the intrapancreatic activation of trypsin (IPAT) or in the pancreatic secretion pathway (PSP) may enhance the risk for RP/CP in patients with CF.

Methods: We enrolled: 48 patients affected by CF complicated by RP/CP and, as controls 35 patients with CF without pancreatitis and 80 unrelated healthy subjects. We tested a panel of 8 genes involved in the IPAT, i.e. PRSS1, PRSS2, SPINK1, CTRC, CASR, CFTR, CTSB and KRT8 and 23 additional genes implicated in the PSP.

Results: We found 14/48 patients (29.2%) with mutations in genes involved in IPAT in the group of CF patients with RP/CP, while mutations in such genes were found in 2/35 (5.7%) patients with CF without pancreatitis and in 3/80 (3.8%) healthy subjects (p < 0.001). Thus, we found mutations in 12 genes of the PSP in 11/48 (22.9%) patients with CF and RP/CP. Overall, 19/48 (39.6%) patients with CF and RP/CP showed one or more mutations in the genes involved in the IPAT and in the PSP while such figure was 4/35 (11.4%) for patients with CF without pancreatitis and 11/80 (13.7%) for healthy controls (p < 0.001).

Conclusions: The trans-heterozygous association between CFTR mutations in genes involved in the pathways of pancreatic enzyme activation and the pancreatic secretion may be risk factors for the development of recurrent or chronic pancreatitis in patients with CF.

Keywords: CFTR gene; Cystic fibrosis; Pancreatic pathways; Recurrent/chronic pancreatitis; Trans-heterozogosity; Trypsin.

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Conflict of interest statement

Ethics approval and consent to participate

The study was approved by the Ethical Committee (Scientific Board of “Bambino Gesù” Children’s Hospital, IRCCS, Rome, Italy) and was conducted in accordance with the Helsinki Declaration.

Consent for publication

The informed consent to participate at this study and for publication of the results was obtained from all patients or from the parents or guardians of minors.

Competing interests

The authors declare they have no competing interests or other interests that might be perceived to influence the results and discussion reported in this paper.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flowchart of the results of molecular analysis in 48 patients affected by CF and recurrent/chronic pancreatitis (a), in 35 patients with CF and without pancreatitis (b) and in 80 healthy subjects (c)
See this image and copyright information in PMC

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