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The cystic fibrosis transmembrane conductance regulator gene and ion channel function in patients with idiopathic pancreatitis

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Abstract

Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations are associated with cystic fibrosis (CF)-related monosymptomatic conditions, including idiopathic pancreatitis. We evaluated prospectively enrolled patients who had idiopathic recurrent acute pancreatitis or idiopathic chronic pancreatitis, healthy controls, CF heterozygotes, and CF patients (pancreatic insufficient or sufficient) for evidence of CFTR gene mutations and abnormalities of ion transport by sweat chloride and nasal potential difference testing. DNA samples from anonymous blood donors were controls for genotyping. At least one CFTR mutation or variant was carried in 18 of 40 patients (45%) with idiopathic chronic pancreatitis and in 6 of 16 patients (38%) with idiopathic recurrent acute pancreatitis but in only 11 of the 50 controls (22%, P=0.005). Most identified mutations were rare and would not be identified in routine genetic screening. CFTR mutations were identified on both alleles in six patient (11%). Ion transport measurements in patients with pancreatitis showed a wide range of results, from the values in patients with classically diagnosed CF to those in the obligate heterozygotes and healthy controls. In general, ion channel measurements correlated with the number and severity of CFTR mutations. Twelve of 56 patients with pancreatitis (21%) fulfilled current clinical criteria for the diagnosis of CF, but CFTR genotyping alone confirmed the diagnosis in only two of these patients. We concluded that extensive genotyping and ion channel testing are useful to confirm or exclude the diagnosis of CF in the majority of patients with idiopathic pancreatitis.

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Acknowledgments

Supported by The National Institutes of Health (NIH-SCOR [NIDDK 5P50 DK49096]), the United States and Canadian Cystic Fibrosis Foundations, American College of Gastroenterology Clinical Research Award to M.D.B., and Canadian Cystic Fibrosis Foundation Research Fellowship to N.A. This research was supported, in part, by a grant (RR01032) to the Beth Israel Deaconess Medical Center General Clinical Research Center from the National Institutes of Health.

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  1. Michele D. Bishop

    Present address: Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA

Authors and Affiliations

  1. Department of Medicine, Beth Israel Deaconess Medical Center, Harvard School of Medicine, Boston, MA, USA

    Michele D. Bishop, Steven D. Freedman, Julie Shea & Isobel Hopper

  2. The Research Institute, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada

    Julian Zielenski, Najma Ahmed, Annie Dupuis, Sheelagh Martin, Lynda Ellis, Mary Corey, John Tzountzouris, Leslie Steele, Peter N. Ray, Lap-Chee Tsui & Peter R. Durie

  3. Department of Medicine, St. Michael’s Hospital, Toronto, ON, M5G 1X8, Canada

    Paul Kortan, Gregory Haber & Christine Ross

  4. Faculty of Medicine, University of Toronto, Toronto, ON, M5G 1X8, Canada

    Julian Zielenski, Najma Ahmed, Mary Corey, Paul Kortan, Gregory Haber, Leslie Steele, Peter N. Ray, Lap-Chee Tsui & Peter R. Durie

  5. Division of Gastroenterology and Nutrition, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada

    Peter R. Durie

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  1. Michele D. Bishop
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Correspondence to Peter R. Durie.

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Bishop, M.D., Freedman, S.D., Zielenski, J. et al. The cystic fibrosis transmembrane conductance regulator gene and ion channel function in patients with idiopathic pancreatitis. Hum Genet 118, 372–381 (2005). https://doi.org/10.1007/s00439-005-0059-z

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