Increased risk of idiopathic chronic pancreatitis in cystic fibrosis carriers.

Published

Journal Article

Cystic fibrosis (CF) is a recessive disease caused by mutations of the CF transmembrane conductance regulator (CFTR) gene. The risk of idiopathic chronic pancreatitis (ICP) is increased in individuals who have CFTR genotypes containing a CF-causing mutation plus a second pathogenic allele. It is unknown whether the risk of ICP is increased in CF carriers who have one CF-causing mutation plus one normal allele. In this study, 52 sporadic cases of ICP were ascertained through the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer. Individuals with pathogenic cationic trypsinogen mutations were excluded. DNA was comprehensively tested for CFTR mutations using a robotically enhanced, multiplexed, and highly redundant form of single-strand conformation polymorphism (SSCP) analysis followed by DNA sequencing. Fifteen subjects had a total of 18 pathogenic CFTR alleles. Eight subjects had common CF-causing mutations. This group included seven CF carriers in whom the second CFTR allele was normal (4.3 times the expected frequency, P=0.0002). Three subjects had compound heterozygotes genotypes containing two pathogenic alleles (31 times the expected frequency, P<0.0001). A variant allele of uncertain significance (p.R75Q) was detected in eight of the 52 ICP subjects and at a similar frequency (13/96) in random donors. ICP differs from other established CFTR-related conditions in that ICP risk is increased in CF carriers who have one documented normal CFTR allele. Having two CFTR mutations imparts a higher relative risk, while having only one mutation imparts a higher attributable risk.

Full Text

Duke Authors

Cited Authors

  • Cohn, JA; Neoptolemos, JP; Feng, J; Yan, J; Jiang, Z; Greenhalf, W; McFaul, C; Mountford, R; Sommer, SS

Published Date

  • October 2005

Published In

Volume / Issue

  • 26 / 4

Start / End Page

  • 303 - 307

PubMed ID

  • 16134171

Pubmed Central ID

  • 16134171

Electronic International Standard Serial Number (EISSN)

  • 1098-1004

International Standard Serial Number (ISSN)

  • 1059-7794

Digital Object Identifier (DOI)

  • 10.1002/humu.20232

Language

  • eng