CFTR, PRSS1 and SPINK1 mutations in the development of pancreatitis in Brazilian patients.
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.
Bernardino
Andrea L Ferreira
AL
Human Genome Research Center, University of São Paulo, São Paulo, Brazil.
Guarita
Dulce Reis
DR
Mott
Carlos Barros
CB
Pedroso
Martha Regina Arcon
MR
Machado
Marcel Cerqueira Cesar
MC
Laudanna
Antonio Atilio
AA
Tani
Claudia Megume
CM
Almeida
Fatima Lovatti
FL
Zatz
Mayana
M
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*
C505032:CFTR protein, human; D015842:Serine Proteinase Inhibitors; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014362:Trypsinogen; C489303:PRSS1 protein, human; D014357:Trypsin