title: Mutation analysis of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, the cationic trypsinogen (PRSS1) gene, and the serine protease inhibitor, Kazal type 1 (SPINK1) gene in patients with alcoholic chronic pancreatitis.
abstract: Susceptibility to alcoholic chronic pancreatitis (ACP) could be genetically determined. Mutations in cationic trypsinogen (PRSS1), cystic fibrosis transmembrane conductance regulator (CFTR), and serine protease inhibitor, Kazal type 1 (SPINK1) genes have been variably associated with both the hereditary and the idiopathic form of chronic pancreatitis (CP). Our aim was to analyze the three genes in ACP patients. Mutational screening was performed in 45 unrelated ACP patients and 34 patients with alcoholic liver disease (ALD). No mutation of PRSS1 was found in ACP and ALD patients. Three mutations of CFTR were detected in four ACP patients with a prevalence (8.9%) not significantly different from that observed (3.0%) in ALD patients and from that expected (3.2%) in our geographical area. Neither compound heterozygotes for CFTR nor trans-heterozygotes for CFTR/SPINK1 were found. One ACP patient (2.2%) was found to carry the most common mutation (N34S) of SPINK1 compared to none of the ALD patients (P=NS). In five other patients (two with ACP and three with ALD) other rare variants, including P55S, were found. In contrast with the hereditary and the idiopathic forms of CP, in which mutations of PRSS1, CFTR, and SPINK1 genes may occur, ACP is still a "gene(s)-orphan" disease. The supposed genetic susceptibility to ACP relies on other yet unknown gene(s) which could affect the alcohol metabolism or modulate the pancreatic inflammatory response to alcohol abuse.
authors.affiliation: Division of Gastroenterology, Casa Sollievo della Sofferenza Hospital, IRCCS, 71013 San Giovanni Rotondo-1, Italy. f.perri@operapadrepio.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Perri
authors.forename: Ada
authors.initials: A
authors.lastname: Piepoli
authors.forename: Pietro
authors.initials: P
authors.lastname: Stanziale
authors.forename: Antonio
authors.initials: A
authors.lastname: Merla
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Zelante
authors.forename: Angelo
authors.initials: A
authors.lastname: Andriulli
mesh_terms: D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D014644:Genetic Variation; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D008297:Male; D008875:Middle Aged; D019512:Pancreatitis, Alcoholic / Q000235:genetics*; D012697:Serine Endopeptidases / Q000235:genetics*; D014359:Trypsin Inhibitor, Kazal Pancreatic
chemical_list: C505032:CFTR protein, human; D002352:Carrier Proteins; C486642:SPINK1 protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014359:Trypsin Inhibitor, Kazal Pancreatic; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases