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Abstract

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and the 5T genotype of the polythymidine tract at the exon 9 splice branch/acceptor site are shown to be associated with chronic pancreatitis in Caucasian patients. In contrast to Western countries, cystic fibrosis is extremely rare in Japan. In this study, we investigated the association of mutations or polymorphisms of the CFTR gene with chronic pancreatitis in Japanese patients. Forty-seven patients with chronic pancreatitis (alcohol-related in 31, idiopathic in 14, and familial in 2) were examined for the deltaF508 and R117H mutations and polymorphisms of intron 8. DNA was extracted from leukocytes. Mutations and polymorphisms were examined by the allele-specific polymerase chain reactions and confirmed by direct sequencing. None of the patients had deltaF508 or R117H mutations in the CFTR gene. All of 47 healthy Japanese showed the homozygous 7T/7T genotype, whereas the frequencies of 5T, 7T, and 9T alleles were 0.043, 0.894, and 0.064 in the patients, respectively. The difference in allele frequency is statistically significant. Therefore, the present study indicates the association of polymorphism of the polythymidine tract in intron 8 of the CFTR gene with chronic pancreatitis in Japanese patients.

CFTR Gene Mutation in Patients with Apparently Idiopathic Pancreatitis: Lack of Phenotype-Genotype Correlation

“…Common CF mutations were found in 14 of the 100 patients with IP (14%) and globally, one CFTR mutation or variant was found in 50% of the patients with IP. This is the highest rate published in the literature (7–43%) [14,16,45,53,54,55,56,57]. This may be explained in part by a more thorough and exhaustive search for mutations using both automated and direct sequencing methods.…”

“…Most studies conclude that this polymorphism does not confer a significant risk of CP [14,16,60]. However, Kimura et al [55] found an association between 5T and CP in Japan. Bishop et al [42] found a 32% rate of 5T allele expression in patients with recurrent acute/chronic pancreatitis and there was a significant difference with the control group.…”