title: Determination of the relative contribution of three genes-the cystic fibrosis transmembrane conductance regulator gene, the cationic trypsinogen gene, and the pancreatic secretory trypsin inhibitor gene-to the etiology of idiopathic chronic pancreatitis.
abstract: In the last 5 years, mutations in three genes, the cystic fibrosis transmembrane conductance regulator (CFTR) gene, the cationic trypsinogen (PRSS1) gene, and the pancreatic secretory trypsin inhibitor (PSTI) gene, have been found to be associated with chronic pancreatitis (CP). In this study, using established mutation screening methods, we systematically analysed the entire coding sequences and all exon/intron junctions of the three genes in 39 patients with idiopathic CP (ICP), with a view to evaluating the relative contribution of each gene to the aetiology of the disease. Our results demonstrate that, firstly, 'gain-of-function' mutations in the PRSS1 gene may occasionally be found in an obvious ICP subject. Secondly, presumably 'loss-of-function' mutations in the PSTI gene appear to be frequent, with a detection rate of at least 10% in ICP and, finally, abnormal CFTR alleles are common: at least 20% of patients carried one of the most common CFTR mutations, and about 10% of patients were compound heterozygotes, having at least one 'mild' allele. Thus, in total, about 30% of ICP patients carried at least one abnormal allele in one of the three genes, and this is the most conservative estimate. Moreover, a trans-heterozygous state with sequence variations in the PSTI/CFTR genes was found in three patients. However, an association between the 5T allele in intron 8 of the CFTR gene and ICP remains unproven.
authors.affiliation: INSERM-EMI 01 15, Génétique Moléculaire et Génétique Epidémiologique, Centre Hospitalier Universitaire, Brest, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Audrézet
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Chen
authors.forename: Cedric
authors.initials: C
authors.lastname: Le Maréchal
authors.forename: Philippe
authors.initials: P
authors.lastname: Ruszniewski
authors.forename: Michel
authors.initials: M
authors.lastname: Robaszkiewicz
authors.forename: Odile
authors.initials: O
authors.lastname: Raguénès
authors.forename: Isabelle
authors.initials: I
authors.lastname: Quéré
authors.forename: Virginie
authors.initials: V
authors.lastname: Scotet
authors.forename: Claude
authors.initials: C
authors.lastname: Férec
mesh_terms: D002908:Chronic Disease; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005602:France; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009154:Mutation; D010195:Pancreatitis / Q000209:etiology / Q000235:genetics*; D014357:Trypsin; D014359:Trypsin Inhibitor, Kazal Pancreatic / Q000235:genetics* / Q000378:metabolism; D014362:Trypsinogen / Q000235:genetics* / Q000378:metabolism
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014359:Trypsin Inhibitor, Kazal Pancreatic; D014362:Trypsinogen; C489303:PRSS1 protein, human; D014357:Trypsin