Clinical ScienceCystic fibrosis gene mutations and pancreatitis risk: Relation to epithelial ion transport and trypsin inhibitor gene mutationsā,āā,ā
Section snippets
Study subjects
Our prior study examined 27 subjects who were identified by reviewing charts of patients referred to Duke University Medical Center from 1991 to 1996, as described.4 Briefly, each subject was white and had multiple episodes of abdominal pain with objective evidence of pancreatitis; we excluded patients with moderate alcohol use (over 15 drinks/week at any time), hereditary pancreatitis by family history, or CF lung disease.4 When subsequent genetic testing diagnosed hereditary pancreatitis15 in
CFTR mutations in individual subjects
Twenty-six CFTR mutations were detected in 17 subjects (Table 2).There were 21 common mutations; 9 were severe (CFsev: ĪF508, N1303K, 621+1G>T) and 12 were mild-variable (CFm-v: 5T, R117H). Among the 9 subjects with severe mutations (nominal CF carriers), 3 had common milder CFTR mutations (nos. 1ā3), 5 had rare mutations that were detected by DNA sequencing (nos. 4ā8), and 1 had a normal second CFTR allele based on DNA sequencing (no. 10). Each of the rare mutations detected in subjects 4ā8 is
Discussion
This study shows that idiopathic chronic pancreatitis is often associated with having 2 CFTR mutations or 1 PSTI mutation. These genotypes occurred in many cases diagnosed by age 50 years (16/32 after excluding hereditary pancreatitis) and in most diagnosed by 21 years old (7/10). Pancreatitis risk was highest in those with 2 CFTR mutations plus N34S.
For CFTR, the greatest risk of pancreatitis is associated with compound heterozygote genotypes containing 1 severe mutation plus 1 mild-variable
Acknowledgements
The authors thank R. Pace and C. Foy for technical assistance, S. Minnix for assistance recruiting subjects, Dr. S. Schmidt for assistance with statistics, and the following physicians for providing clinical data about their patients: J. D. Bornstein, J. Baillie, M. S. Branch, and W. R. Treem (Duke University Medical Center), T. Desai (Beaumont Hospital, Royal Oaks, MI), S. Shutz (Wilford Hall Medical Center, Lackland AFB, TX), T. H. Baron (University of Alabama Medical Center, Birmingham, AL),
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Supported in part by grants from the Department of Veterans Affairs, the Cystic Fibrosis Foundation, and the National Institutes of Health.
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Address requests for reprints to: Jonathan A. Cohn, M.D., Box 3378, Duke University Medical Center, Durham, North Carolina 27710. e-mail: [email protected]; fax: (919) 684-4983.
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Drs. Noone and Zhou contributed equally to this work.