title: CFTR, PRSS1 and SPINK1 mutations in the development of pancreatitis in Brazilian patients.
abstract: BACKGROUND
  Mutations in cystic fibrosis transmembrane conductance regulator (CFTR), in cationic trypsinogen (PRSS1) and in serine protease inhibitor Kazal type 1 (SPINK1) genes have been associated with chronic pancreatitis (alcohol related, idiopathic and hereditary). However, the inheritance pattern is still not clear.
  
  
  METHODS
  Eighty-two unrelated Brazilian patients with chronic pancreatitis (alcohol-related disease in 64, idiopathic disease in 16, and hereditary disease in 2). Two hundred unrelated individuals with an ethnic distribution comparable to the patients were studied as controls.
  
  
  METHODS
  Detection of mutations in CFTR, PRSS1, and SPINK1 genes.
  
  
  RESULTS
  Mutations in the CFTR gene were found in 8 patients (9.8%) with chronic pancreatitis, 5 of them with idiopathic disease. Interestingly, the only clinical symptom in a male patient in the alcoholic group, who was a compound heterozygote (DeltaF508/R170C) for two CFTR mutations, was pancreatitis without infertility or pulmonary involvement. In the PRSS1 gene, the E79K change in exon 3 was found in one patient (1.2%) with alcohol-related chronic pancreatitis. Four different alterations were identified in the SPINK1 gene.
  
  
  CONCLUSIONS
  Mutations in the CFTR gene represent the major cause of idiopathic chronic pancreatitis in Brazilian patients. No mutation was found in the PRSS1 gene among our patients suggesting further genetic heterogeneity for hereditary and idiopathic chronic pancreatitis. Interestingly, the most frequent SPINK1 N34S mutation was not present in patients or controls. Moreover, the -253C allele for the SPINK1 gene was significantly more frequent in patients than controls (P=0.004), suggesting that it might represent a risk factor for the development of pancreatitis in our population.
authors.affiliation: Human Genome Research Center, University of São Paulo, São Paulo, Brazil.
authors.forename: Andrea L Ferreira
authors.initials: AL
authors.lastname: Bernardino
authors.forename: Dulce Reis
authors.initials: DR
authors.lastname: Guarita
authors.forename: Carlos Barros
authors.initials: CB
authors.lastname: Mott
authors.forename: Martha Regina Arcon
authors.initials: MR
authors.lastname: Pedroso
authors.forename: Marcel Cerqueira Cesar
authors.initials: MC
authors.lastname: Machado
authors.forename: Antonio Atilio
authors.initials: AA
authors.lastname: Laudanna
authors.forename: Claudia Megume
authors.initials: CM
authors.lastname: Tani
authors.forename: Fatima Lovatti
authors.initials: FL
authors.lastname: Almeida
authors.forename: Mayana
authors.initials: M
authors.lastname: Zatz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001938:Brazil / Q000453:epidemiology; D002648:Child; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010195:Pancreatitis / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D019512:Pancreatitis, Alcoholic / Q000235:genetics; D015842:Serine Proteinase Inhibitors / Q000235:genetics; D014357:Trypsin; D014362:Trypsinogen / Q000235:genetics*
chemical_list: C505032:CFTR protein, human; D015842:Serine Proteinase Inhibitors; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014362:Trypsinogen; C489303:PRSS1 protein, human; D014357:Trypsin