title: CFTR and/or pancreatitis susceptibility genes mutations as risk factors of pancreatitis in cystic fibrosis patients?
abstract: OBJECTIVE
  Currently, factors that promote the occurrence of pancreatitis episodes in patients affected with cystic fibrosis (CF) and pancreatic sufficiency (PS) are largely unknown.
  
  
  METHODS
  Six genes involved in pancreatitis or in ion transport into the pancreatic duct were investigated by next generation sequencing in 59 adult CF-PS patients with two identified CF mutations. Data on predisposing environmental factors were also recorded.
  
  
  RESULTS
  19 experienced at least one episode of acute pancreatitis (AP) (AP+) and 40 patients did not (AP-). No influence of environmental factor was evidenced. No specific CFTR genotype was found predictive of pancreatitis. Patients sharing the same CFTR genotype may or may not experience AP episodes. Frequent and rare missense variants were found in 78.9% patients in group AP+ and 67.5% in group AP- but a few of them were pathogenic.
  
  
  CONCLUSIONS
  AP or recurrent AP (RAP) is a frequent complication in our series of adult CF-PS patients. The majority of mild CFTR mutations found in group AP+ were located in the first transmembrane region. No clear other genetic factor could be found predictive of AP/RAP. Further experiments in large homogenous cohorts of CF-PS patients, including whole genome sequencing, may identify genetic predisposing factors to pancreatitis.
authors.affiliation: AP-HP, Laboratoire de Génétique et Biologie Moléculaires, HU Paris Centre, Site Cochin, France.
authors.forename: Natacha
authors.initials: N
authors.lastname: Gaitch
authors.affiliation: Service de Pneumologie, HU Paris Centre, Site Cochin and Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Hubert
authors.affiliation: AP-HP, Laboratoire de Génétique et Biologie Moléculaires, HU Paris Centre, Site Cochin, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Gameiro
authors.affiliation: Service de Pneumologie, HU Paris Centre, Site Cochin and Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Pierre-Régis
authors.initials: PR
authors.lastname: Burgel
authors.affiliation: AP-HP, Laboratoire de Génétique et Biologie Moléculaires, HU Paris Centre, Site Cochin, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Houriez
authors.affiliation: AP-HP, Laboratoire de Génétique et Biologie Moléculaires, HU Paris Centre, Site Cochin, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Martinez
authors.affiliation: Service de Pneumologie, HU Paris Centre, Site Cochin and Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Honoré
authors.affiliation: Service de Pneumologie, HU Paris Centre, Site Cochin and Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Chapron
authors.affiliation: Service de Pneumologie, HU Paris Centre, Site Cochin and Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Reem
authors.initials: R
authors.lastname: Kanaan
authors.affiliation: Service de Pneumologie, HU Paris Centre, Site Cochin and Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Dusser
authors.affiliation: AP-HP, Laboratoire de Génétique et Biologie Moléculaires, HU Paris Centre, Site Cochin, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Girodon
authors.affiliation: AP-HP, Laboratoire de Génétique et Biologie Moléculaires, HU Paris Centre, Site Cochin, France; Université Paris Descartes Paris, Institut Cochin, INSERM U1016, Paris, France. Electronic address: thierry.bienvenu@inserm.fr.
authors.forename: Thierry
authors.initials: T
authors.lastname: Bienvenu
mesh_terms: D000328:Adult; D017668:Age of Onset; D003550:Cystic Fibrosis / Q000150:complications* / Q000453:epidemiology / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010183:Pancreatic Ducts / Q000378:metabolism; D010195:Pancreatitis / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator
keywords: Bicarbonate; CFTR; Cystic fibrosis; Modifier genes; Next Generation Sequencing; Pancreatitis