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

Valentina Maria Sofia, Cecilia Surace, Vito Terlizzi, Letizia Da Sacco, Federico Alghisi, Antonella Angiolillo, Cesare Braggion, Natalia Cirilli, Carla Colombo, Antonella Di Lullo, Rita Padoan, Serena Quattrucci, Valeria Raia, Giuseppe Tuccio, Federica Zarrilli, Anna Cristina Tomaiuolo, Antonio Novelli, Vincenzina Lucidi, Marco Lucarelli, Giuseppe CastaldoAdriano Angioni

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)38
Number of pages10
JournalMolecular medicine (Cambridge, Mass.)
Volume24
Issue number1
DOIs
Publication statusPublished - Jul 27 2018

Fingerprint

Chronic Pancreatitis
Cystic Fibrosis
Mutation
Secretory Pathway
Trypsin
Genes
Pancreatitis
Healthy Volunteers
Enzyme Activation

Cite this

Trans-heterozygosity for mutations enhances the risk of recurrent/chronic pancreatitis in patients with Cystic Fibrosis. / Sofia, Valentina Maria; Surace, Cecilia; Terlizzi, Vito; Da Sacco, Letizia; Alghisi, Federico; Angiolillo, Antonella; Braggion, Cesare; Cirilli, Natalia; Colombo, Carla; Di Lullo, Antonella; Padoan, Rita; Quattrucci, Serena; Raia, Valeria; Tuccio, Giuseppe; Zarrilli, Federica; Tomaiuolo, Anna Cristina; Novelli, Antonio; Lucidi, Vincenzina; Lucarelli, Marco; Castaldo, Giuseppe; Angioni, Adriano.

In: Molecular medicine (Cambridge, Mass.), Vol. 24, No. 1, 27.07.2018, p. 38.

Research output: Contribution to journalArticle

Sofia, VM, Surace, C, Terlizzi, V, Da Sacco, L, Alghisi, F, Angiolillo, A, Braggion, C, Cirilli, N, Colombo, C, Di Lullo, A, Padoan, R, Quattrucci, S, Raia, V, Tuccio, G, Zarrilli, F, Tomaiuolo, AC, Novelli, A, Lucidi, V, Lucarelli, M, Castaldo, G & Angioni, A 2018, 'Trans-heterozygosity for mutations enhances the risk of recurrent/chronic pancreatitis in patients with Cystic Fibrosis', Molecular medicine (Cambridge, Mass.), vol. 24, no. 1, pp. 38. https://doi.org/10.1186/s10020-018-0041-6
Sofia, Valentina Maria ; Surace, Cecilia ; Terlizzi, Vito ; Da Sacco, Letizia ; Alghisi, Federico ; Angiolillo, Antonella ; Braggion, Cesare ; Cirilli, Natalia ; Colombo, Carla ; Di Lullo, Antonella ; Padoan, Rita ; Quattrucci, Serena ; Raia, Valeria ; Tuccio, Giuseppe ; Zarrilli, Federica ; Tomaiuolo, Anna Cristina ; Novelli, Antonio ; Lucidi, Vincenzina ; Lucarelli, Marco ; Castaldo, Giuseppe ; Angioni, Adriano. / Trans-heterozygosity for mutations enhances the risk of recurrent/chronic pancreatitis in patients with Cystic Fibrosis. In: Molecular medicine (Cambridge, Mass.). 2018 ; Vol. 24, No. 1. pp. 38.
@article{0ca2b5d1d25e4d1798a68e70f3eb5211,
title = "Trans-heterozygosity for mutations enhances the risk of recurrent/chronic pancreatitis in patients with Cystic Fibrosis",
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.",
author = "Sofia, {Valentina Maria} and Cecilia Surace and Vito Terlizzi and {Da Sacco}, Letizia and Federico Alghisi and Antonella Angiolillo and Cesare Braggion and Natalia Cirilli and Carla Colombo and {Di Lullo}, Antonella and Rita Padoan and Serena Quattrucci and Valeria Raia and Giuseppe Tuccio and Federica Zarrilli and Tomaiuolo, {Anna Cristina} and Antonio Novelli and Vincenzina Lucidi and Marco Lucarelli and Giuseppe Castaldo and Adriano Angioni",
year = "2018",
month = "7",
day = "27",
doi = "10.1186/s10020-018-0041-6",
language = "English",
volume = "24",
pages = "38",
journal = "Molecular Medicine",
issn = "1076-1551",
publisher = "Feinstein Institute for Medical Research",
number = "1",

}

TY - JOUR

T1 - Trans-heterozygosity for mutations enhances the risk of recurrent/chronic pancreatitis in patients with Cystic Fibrosis

AU - Sofia, Valentina Maria

AU - Surace, Cecilia

AU - Terlizzi, Vito

AU - Da Sacco, Letizia

AU - Alghisi, Federico

AU - Angiolillo, Antonella

AU - Braggion, Cesare

AU - Cirilli, Natalia

AU - Colombo, Carla

AU - Di Lullo, Antonella

AU - Padoan, Rita

AU - Quattrucci, Serena

AU - Raia, Valeria

AU - Tuccio, Giuseppe

AU - Zarrilli, Federica

AU - Tomaiuolo, Anna Cristina

AU - Novelli, Antonio

AU - Lucidi, Vincenzina

AU - Lucarelli, Marco

AU - Castaldo, Giuseppe

AU - Angioni, Adriano

PY - 2018/7/27

Y1 - 2018/7/27

N2 - 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.

AB - 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.

U2 - 10.1186/s10020-018-0041-6

DO - 10.1186/s10020-018-0041-6

M3 - Article

C2 - 30134826

VL - 24

SP - 38

JO - Molecular Medicine

JF - Molecular Medicine

SN - 1076-1551

IS - 1

ER -