FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Volume 339:645-652 September 3, 1998 Number 10 Next

	Full Text PDF Editorial by Durie, P. R. Letters Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited Related Article by Malats, N. PubMed Citation

ABSTRACT

Background The pancreatic lesions of cystic fibrosis develop in utero and closely resemble those of chronic pancreatitis. Therefore, we hypothesized that mutations of the cystic fibrosis transmembrane conductance regulator (CF TR ) gene may be more common than expected among patients with chronic pancreatitis.

Methods We studied 134 consecutive patients with chronic pancreatitis (alcohol-related disease in 71, hyperparathyroidism in 2, hypertriglyceridemia in 1, and idiopathic disease in 60). We examined DNA for 22 mutations of the CF TR gene that together account for 95 percent of all mutations in patients with cystic fibrosis in the northwest of England. We also determined the length of the noncoding sequence of thymidines in intron 8, since the shorter the sequence, the lower the proportion of normal CFTR messenger RNA.

Results The 94 male and 40 female patients ranged in age from 16 to 86 years. None had a mutation on both copies of the CF TR gene. Eighteen patients (13.4 percent), including 12 without alcoholism, had a CF TR mutation on one chromosome, as compared with a frequency of 5.3 percent among 600 local unrelated partners of persons with a family history of cystic fibrosis (P<0.001). A total of 10.4 percent of the patients had the 5T allele in intron 8 (14 of 134), which is twice the expected frequency (P=0.008). Four patients were heterozygous for both a CF TR mutation and the 5T allele. Patients with a CF TR mutation were younger than those with no mutations (P=0.03). None had the combination of sinopulmonary disease, high sweat electrolyte concentrations, and low nasal potential-difference values that are diagnostic of cystic fibrosis.

Conclusions Mutations of the CF TR gene and the 5T genotype are associated with chronic pancreatitis.

Source Information

From the Pancreato-Biliary Unit (N.S., J.P.) and University Department of Medicine (J.B.), Manchester Royal Infirmary; and the Regional Genetic Service, Royal Manchester Children's Hospital (M. Schwarz, G.M., A.H., M. Super) — both in Manchester, United Kingdom.

Address reprint requests to Dr. Braganza at Manchester Royal Infirmary, Oxford Rd., Manchester M13 9WL, United Kingdom.

Full Text of this Article

Related Letters:

Correction: Mutations of the Cystic Fibrosis Gene in Patients with Chronic Pancreatitis
Malats N., Real F. X., Sharer N. M., Schwartz M. J.
Extract | Full Text  
N Engl J Med 1999; 340:1592-1593, May 20, 1999. Correspondence

Mutations of the Cystic Fibrosis Gene and Pancreatitis
Ren C. L., Sharer N., Schwartz M., Cohn J. A., Silverman L. M., Knowles M. R.
Extract | Full Text  
N Engl J Med 1999; 340:238-239, Jan 21, 1999. Correspondence

This article has been cited by other articles:

• Yadav, D., Hawes, R. H., Brand, R. E., Anderson, M. A., Money, M. E., Banks, P. A., Bishop, M. D., Baillie, J., Sherman, S., DiSario, J., Burton, F. R., Gardner, T. B., Amann, S. T., Gelrud, A., Lawrence, C., Elinoff, B., Greer, J. B., O'Connell, M., Barmada, M. M., Slivka, A., Whitcomb, D. C., for the North American Pancreatic Study Group, (2009). Alcohol Consumption, Cigarette Smoking, and the Risk of Recurrent Acute and Chronic Pancreatitis. Arch Intern Med 169: 1035-1045 [Abstract] [Full Text]  
• Audrezet, M.-P., Dabricot, A., Le Marechal, C., Ferec, C. (2008). Validation of High-Resolution DNA Melting Analysis for Mutation Scanning of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Gene. J. Mol. Diagn. 10: 424-434 [Abstract] [Full Text]  
• Costa, C., Costa, J.-M., Martin, J., Boissier, B., Goossens, M., Girodon, E. (2008). Multiplex Allele-Specific Fluorescent PCR for Haplotyping the IVS8 (TG)m(T)n Locus in the CFTR Gene. Clin. Chem. 54: 1564-1567 [Abstract] [Full Text]  
• Callery, M. P., Freedman, S. D. (2008). A 21-Year-Old Man With Chronic Pancreatitis. JAMA 299: 1588-1594 [Abstract] [Full Text]  
• Chang, Y.-T., Chang, M.-C., Su, T.-C., Liang, P.-C., Su, Y.-N., Kuo, C.-H., Wei, S.-C., Wong, J.-M. (2008). Association of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mutation/Variant/Haplotype and Tumor Necrosis Factor (TNF) Promoter Polymorphism in Hyperlipidemic Pancreatitis. Clin. Chem. 54: 131-138 [Abstract] [Full Text]  
• Osterreicher, C. H., Schultheiss, J., Wehler, M., Homann, N., Hellerbrand, C., Kunzli, B., Friess, H., Seitz, H. K., Stickel, F. (2007). Genetic polymorphisms of manganese-superoxide dismutase and glutathione-S-transferase in chronic alcoholic pancreatitis. Mutagenesis 22: 305-310 [Abstract] [Full Text]  
• Wilschanski, M., Durie, P. R (2007). Patterns of GI disease in adulthood associated with mutations in the CFTR gene. Gut 56: 1153-1163 [Full Text]  
• Ratbi, I., Legendre, M., Niel, F., Martin, J., Soufir, J.-C., Izard, V., Costes, B., Costa, C., Goossens, M., Girodon, E. (2007). Detection of cystic fibrosis transmembrane conductance regulator (CFTR) gene rearrangements enriches the mutation spectrum in congenital bilateral absence of the vas deferens and impacts on genetic counselling. Hum Reprod 22: 1285-1291 [Abstract] [Full Text]  
• Sidani, S. M., Kirchhoff, P., Socrates, T., Stelter, L., Ferreira, E., Caputo, C., Roberts, K. E., Bell, R. L., Egan, M. E., Geibel, J. P. (2007). {Delta}F508 Mutation Results in Impaired Gastric Acid Secretion. J. Biol. Chem. 282: 6068-6074 [Abstract] [Full Text]  
• Poolman, E. M, Galvani, A. P (2007). Evaluating candidate agents of selective pressure for cystic fibrosis. J R Soc Interface 4: 91-98 [Abstract] [Full Text]  
• Yamamoto, M., Otani, M., Otsuki, M. (2006). A new model of chronic pancreatitis in rats.. Am. J. Physiol. Gastrointest. Liver Physiol. 291: G700-G708 [Abstract] [Full Text]  
• Wilschanski, M., Dupuis, A., Ellis, L., Jarvi, K., Zielenski, J., Tullis, E., Martin, S., Corey, M., Tsui, L.-C., Durie, P. (2006). Mutations in the Cystic Fibrosis Transmembrane Regulator Gene and In Vivo Transepithelial Potentials. Am. J. Respir. Crit. Care Med. 174: 787-794 [Abstract] [Full Text]  
• Faa, V., Bettoli, P. P., Demurtas, M., Zanda, M., Ferri, V., Cao, A., Rosatelli, M. C. (2006). A New Insertion/Deletion of the Cystic Fibrosis Transmembrane Conductance Regulator Gene Accounts for 3.4% of Cystic Fibrosis Mutations in Sardinia: Implications for Population Screening. J. Mol. Diagn. 8: 499-503 [Abstract] [Full Text]  
• Hezel, A. F., Kimmelman, A. C., Stanger, B. Z., Bardeesy, N., DePinho, R. A. (2006). Genetics and biology of pancreatic ductal adenocarcinoma.. Genes Dev. 20: 1218-1249 [Abstract] [Full Text]  
• Sanchez-Fermin, P., Ukleja, A., Cruz-Correa, M. (2006). Successful Long-Term Jejunostomy Feedings in Relapsing Pancreatitis: A Case Report. JPEN J Parenter Enteral Nutr 30: 251-253 [Abstract] [Full Text]  
• McWilliams, R, Highsmith, W E, Rabe, K G, de Andrade, M, Tordsen, L A, Holtegaard, L M, Petersen, G M (2005). Cystic fibrosis transmembrane regulator gene carrier status is a risk factor for young onset pancreatic adenocarcinoma. Gut 54: 1661-1662 [Full Text]  
• Verlaan, M, Drenth, J P H, Truninger, K, Koudova, M, Schulz, H-U, Bargetzi, M, Kunzli, B, Friess, H, Cerny, M, Kage, A, Landt, O, te Morsche, R H M, Rosendahl, J, Luck, W, Nickel, R, Halangk, J, Becker, M, Macek, M Jr, Jansen, J B M J, Witt, H (2005). Polymorphisms of UDP-glucuronosyltransferase 1A7 are not involved in pancreatic diseases. J. Med. Genet. 42: e62-e62 [Abstract] [Full Text]  
• Weiss, F U, Simon, P, Bogdanova, N, Mayerle, J, Dworniczak, B, Horst, J, Lerch, M M (2005). Complete cystic fibrosis transmembrane conductance regulator gene sequencing in patients with idiopathic chronic pancreatitis and controls. Gut 54: 1456-1460 [Abstract] [Full Text]  
• Howell, W M, Pead, P J, Shek, F W, Rose-Zerilli, M J, Armstrong, T, Johnson, C D, Fine, D R, Iredale, J P, Bateman, A C (2005). Influence of cytokine and ICAM-1 gene polymorphisms on susceptibility to chronic pancreatitis. J. Clin. Pathol. 58: 595-599 [Abstract] [Full Text]  
• Rowe, S. M., Miller, S., Sorscher, E. J. (2005). Cystic Fibrosis. NEJM 352: 1992-2001 [Full Text]  
• Idris, M M, Bhaskar, S, Reddy, D N, Mani, K R, Rao, G V, Singh, L, Chandak, G R (2005). Mutations in anionic trypsinogen gene are not associated with tropical calcific pancreatitis. Gut 54: 728-729 [Full Text]  
• De Boeck, K., Weren, M., Proesmans, M., Kerem, E. (2005). Pancreatitis Among Patients With Cystic Fibrosis: Correlation With Pancreatic Status and Genotype. Pediatrics 115: e463-e469 [Abstract] [Full Text]  
• Wang, X., Kim, J., McWilliams, R., Cutting, G. R. (2005). Increased Prevalence of Chronic Rhinosinusitis in Carriers of a Cystic Fibrosis Mutation. Arch Otolaryngol Head Neck Surg 131: 237-240 [Abstract] [Full Text]  
• Whitcomb, D C (2004). Value of genetic testing in the management of pancreatitis. Gut 53: 1710-1717 [Full Text]  
• Niel, F, Martin, J, Dastot-Le Moal, F, Costes, B, Boissier, B, Delattre, V, Goossens, M, Girodon, E (2004). Rapid detection of CFTR gene rearrangements impacts on genetic counselling in cystic fibrosis. J. Med. Genet. 41: e118-e118 [Full Text]  
• Southernl, K W, Peckham, D (2004). Establishing a diagnosis of cystic fibrosis. Chronic Respiratory Disease 1: 205-210 [Abstract]  
• Zaman, M. M., Gelrud, A., Junaidi, O., Regan, M. M., Warny, M., Shea, J. C., Kelly, C., O'Sullivan, B. P., Freedman, S. D. (2004). Interleukin 8 Secretion from Monocytes of Subjects Heterozygous for the {Delta}F508 Cystic Fibrosis Transmembrane Conductance Regulator Gene Mutation Is Altered. CVI 11: 819-824 [Abstract] [Full Text]  
• Chandak, G R, Idris, M M, Reddy, D N, Mani, K R, Bhaskar, S, Rao, G V, Singh, L (2004). Absence of PRSS1 mutations and association of SPINK1 trypsin inhibitor mutations in hereditary and non-hereditary chronic pancreatitis. Gut 53: 723-728 [Abstract] [Full Text]  
• Fujiki, K, Ishiguro, H, Ko, S B., Mizuno, N, Suzuki, Y, Takemura, T, Yamamoto, A, Yoshikawa, T, Kitagawa, M, Hayakawa, T, Sakai, Y, Takayama, T, Saito, M, Kondo, T, Naruse, S (2004). Genetic evidence for CFTR dysfunction in Japanese: background for chronic pancreatitis. J. Med. Genet. 41: e55-e55 [Full Text]  
• Freedman, S. D., Blanco, P. G., Zaman, M. M., Shea, J. C., Ollero, M., Hopper, I. K., Weed, D. A., Gelrud, A., Regan, M. M., Laposata, M., Alvarez, J. G., O'Sullivan, B. P. (2004). Association of Cystic Fibrosis with Abnormalities in Fatty Acid Metabolism. NEJM 350: 560-569 [Abstract] [Full Text]  
• Lee, J. H., Choi, J. H., Namkung, W., Hanrahan, J. W., Chang, J., Song, S. Y., Park, S. W., Kim, D. S., Yoon, J.-H., Suh, Y., Jang, I.-J., Nam, J. H., Kim, S. J., Cho, M.-O., Lee, J.-E., Kim, K. H., Lee, M. G. (2003). A haplotype-based molecular analysis of CFTR mutations associated with respiratory and pancreatic diseases. Hum Mol Genet 12: 2321-2332 [Abstract] [Full Text]  
• Fernandez-del Castillo, C. F., Sahani, D. V., Lauwers, G. Y. (2003). Case 27-2003 - A 36-Year-Old Man with Recurrent Epigastric Pain and Elevated Amylase Levels. NEJM 349: 893-901 [Full Text]  
• Ninis, V N, Kylync, M O, Kandemir, M, Dathly, E, Tolun, A (2003). High frequency of T9 and CFTR mutations in children with idiopathic bronchiectasis. J. Med. Genet. 40: 530-535 [Full Text]  
• Witt, H (2003). Chronic pancreatitis and cystic fibrosis. Gut 52: ii31-41 [Abstract] [Full Text]  
• Witt, H (2002). The SPINK in chronic pancreatitis: similar finds, different minds. Gut 50: 590-591 [Full Text]  
• Threadgold, J, Greenhalf, W, Ellis, I, Howes, N, Lerch, M M, Simon, P, Jansen, J, Charnley, R, Laugier, R, Frulloni, L, Olah, A, Delhaye, M, Ihse, I, Schaffalitzky de Muckadell, O B, Andren-Sandberg, A, Imrie, C W, Martinek, J, Gress, T M, Mountford, R, Whitcomb, D, Neoptolemos, J P (2002). The N34S mutation of SPINK1 (PSTI) is associated with a familial pattern of idiopathic chronic pancreatitis but does not cause the disease. Gut 50: 675-681 [Abstract] [Full Text]  
• Drenth, J P H, te Morsche, R, Jansen, J B M J (2002). Mutations in serine protease inhibitor Kazal type 1 are strongly associated with chronic pancreatitis. Gut 50: 687-692 [Abstract] [Full Text]  
• Chandak, G R, Idris, M M, Reddy, D N, Bhaskar, S, Sriram, P V J, Singh, L (2002). Mutations in the pancreatic secretory trypsin inhibitor gene (PSTI/SPINK1) rather than the cationic trypsinogen gene (PRSS1) are significantly associated with tropical calcific pancreatitis. J. Med. Genet. 39: 347-351 [Full Text]  
• LEBECQUE, P., LEAL, T., DE BOECK, C., JASPERS, M., CUPPENS, H., CASSIMAN, J.-J. (2002). Mutations of the Cystic Fibrosis Gene and Intermediate Sweat Chloride Levels in Children. Am. J. Respir. Crit. Care Med. 165: 757-761 [Abstract] [Full Text]  
• OCKENGA, J, STUHRMANN, M, MANNS, M P, ESTIVILL, X, CASALS, T, MALATS, N, PORTA, M, GUARNER, L, REAL, F X (2001). Evaluation of the role of CFTR in alcohol related pancreatic disease Reply. Gut 49: 312a-313 [Full Text]  
• Doull, I. J M (2001). Recent advances: Recent advances in cystic fibrosis. Arch. Dis. Child. 85: 62-66 [Abstract] [Full Text]  
• Wilschanski, M., Famini, H., Strauss-Liviatan, N., Rivlin, J., Blau, H., Bibi, H., Bentur, L., Yahav, Y., Springer, H., Kramer, M.R., Klar, A., Ilani, A., Kerem, B., Kerem, E. (2001). Nasal potential difference measurements in patients with atypical cystic fibrosis. Eur Respir J 17: 1208-1215 [Abstract] [Full Text]  
• Boyle, M. P. (2001). Minocycline-Induced Pancreatitis in Cystic Fibrosis. Chest 119: 1283-1285 [Abstract] [Full Text]  
• CASTELLANI, C., BENETAZZO, M. G., TAMANINI, A., BEGNINI, A., MASTELLA, G., PIGNATTI, P. (2001). Analysis of the entire coding region of the cystic fibrosis transmembrane regulator gene in neonatal hypertrypsinaemia with normal sweat test. J. Med. Genet. 38: 202-205 [Full Text]  
• Howes, N, Greenhalf, W, Rutherford, S, O'Donnell, M, Mountford, R, Ellis, I, Whitcomb, D, Imrie, C, Drumm, B, Neoptolemos, J P (2001). A new polymorphism for the RI22H mutation in hereditary pancreatitis. Gut 48: 247-250 [Abstract] [Full Text]  
• HUGHES, D., DÖRK, T., STUHRMANN, M., GRAHAM, C. (2001). Mutation and haplotype analysis of the CFTR gene in atypically mild cystic fibrosis patients from Northern Ireland. J. Med. Genet. 38: 136-139 [Full Text]  
• Malats, N, Casals, T, Porta, M, Guarner, L, Estivill, X, Real, F X (2001). Cystic fibrosis transmembrane regulator (CFTR) Delta F508 mutation and 5T allele in patients with chronic pancreatitis and exocrine pancreatic cancer. Gut 48: 70-74 [Abstract] [Full Text]  
• PERSU, A., DEVUYST, O., LANNOY, N., MATERNE, R., BROSNAHAN, G., GABOW, P. A., PIRSON, Y., VERELLEN-DUMOULIN, C. (2000). CF Gene and Cystic Fibrosis Transmembrane Conductance Regulator Expression in Autosomal Dominant Polycystic Kidney Disease. J. Am. Soc. Nephrol. 11: 2285-2296 [Abstract] [Full Text]  
• NOONE, P. G., PUE, C. A., ZHOU, Z., FRIEDMAN, K. J., WAKELING, E. L., GANESHANANTHAN, M., SIMON, R. H., SILVERMAN, L. M., KNOWLES, M. R. (2000). Lung Disease Associated with the IVS8 5T Allele of the CFTR Gene. Am. J. Respir. Crit. Care Med. 162: 1919-1924 [Abstract] [Full Text]  
• ZSEMBERY, A., STRAZZABOSCO, M., GRAF, J. (2000). Ca2+-activated Cl- channels can substitute for CFTR in stimulation of pancreatic duct bicarbonate secretion. FASEB J. 14: 2345-2356 [Abstract] [Full Text]  
• MASSIE, J., DU SART, D., FORSHAW, K., CARLIN, J., FORREST, S M (2000). The relationship between neonatal immunoreactive trypsinogen, Delta F508, and IVS8-5T. J. Med. Genet. 37: 629-632 [Full Text]  
• Casals, T., Bassas, L., Egozcue, S., Ramos, M. D., Gimenez, J., Segura, A., Garcia, F., Carrera, M., Larriba, S., Sarquella, J., Estivill, X. (2000). Heterogeneity for mutations in the CFTR gene and clinical correlations in patients with congenital absence of the vas deferens. Hum Reprod 15: 1476-1483 [Abstract] [Full Text]  
• DODGE, J A (2000). Fibrosing colonopathy. Gut 46: 152-153 [Full Text]  
• Bansi, D S, Price, A, Russell, C, Sarner, M (2000). Fibrosing colonopathy in an adult owing to over use of pancreatic enzyme supplements. Gut 46: 283-285 [Abstract] [Full Text]  
• Mak, V., Zielenski, J., Tsui, L.-C., Durie, P., Zini, A., Martin, S., Longley, T. B., Jarvi, K. A. (2000). Cystic fibrosis gene mutations and infertile men with primary testicular failure. Hum Reprod 15: 436-439 [Abstract] [Full Text]  
• PALLARES-RUIZ, N, CARLES, S, GEORGES, M D., GUITTARD, C, CLAUSTRES, M, LARREY, D, PAGEAUX, G (2000). Is isolated idiopathic pancreatitis associated with CFTR mutations?. Gut 46: 140b-140 [Full Text]  
• CHEN, J.-M., MERCIER, B., AUDREZET, M.-P., FEREC, C. (2000). Mutational analysis of the human pancreatic secretory trypsin inhibitor (PSTI) gene in hereditary and sporadic chronic pancreatitis. J. Med. Genet. 37: 67-69 [Full Text]  
• Brugge, W. R., Dam, J. V. (1999). Pancreatic and Biliary Endoscopy. NEJM 341: 1808-1816 [Full Text]  
• Wyllie, R. (1999). Gastrointestinal Manifestations of Cystic Fibrosis. CLIN PEDIATR 38: 735-738  
• Greenberger, N. J. (1999). Update in Gastroenterology. ANN INTERN MED 131: 445-452 [Full Text]  
• Mak, V., Zielenski, J., Tsui, L.-C., Durie, P., Zini, A., Martin, S., Longley, T. B., Jarvi, K. A. (1999). Proportion of Cystic Fibrosis Gene Mutations Not Detected by Routine Testing in Men With Obstructive Azoospermia. JAMA 281: 2217-2224 [Abstract] [Full Text]  
• Malats, N., Real, F. X., Sharer, N. M., Schwartz, M. J. (1999). Correction: Mutations of the Cystic Fibrosis Gene in Patients with Chronic Pancreatitis. NEJM 340: 1592-1593 [Full Text]  
• SUPER, M. (1999). Can manifesting heterozygotes have cystic fibrosis?. Thorax 54: 194-195 [Full Text]  
• Ren, C. L., Sharer, N., Schwartz, M., Cohn, J. A., Silverman, L. M., Knowles, M. R. (1999). Mutations of the Cystic Fibrosis Gene and Pancreatitis. NEJM 340: 238-239 [Full Text]  
• (1998). Pancreatitis and Cystic Fibrosis Mutations. JWatch General 1998: 5-5 [Full Text]  
• Durie, P. R. (1998). Pancreatitis and Mutations of the Cystic Fibrosis Gene. NEJM 339: 687-688 [Full Text]