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CFTR gene mutations in pancreatitis: Frequency and clinical manifestations in an Austrian patient cohort

CFTR Genmutationen und Pankreatitis: Häufigkeit und klinische Präsentation in einer österreichischen Patientenkohorte

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Zusammenfassung

HINTERGRUND/ZIELE: Patienten mit chronischer Pankreatitis haben häufiger Mutationen im cystic fibrosis transmembrane regulator (CFTR) als die Durschnittsbevölkerung (Heterozygote CFTR Mutationen bei Pankreatitis Patienten 13–37% vs. 3,2% in der Europäischen Bevölkerung). Das Ziel dieser Studie war zu klären, ob sich Patienten mit CFTR Mutationen klinisch von Pankreatitis-Patienten ohne CFTR Mutation unterscheiden. PATIENTEN UND METHODE: Eine Kohorte von 133 Patienten mit Pankreatitis wurde mittels multiplex PCR und Sequenzierung auf die 30 häufigsten CFTR Genmutationen getestet. Gemäß den Kriterien der Japanischen Pankreas Gesellschaft wurde die Pankreatitis als 'acute', 'definitive chronic' or 'possible chronic' klassifiziert. Eine ätiologische Zuordnung erfolgte aufgrund der TIGAR-O Klassifikation in toxische, idiopathische, genetische, autoimmune und rekurrente bzw. obstruktive Pankreatitis. RESULTATE: In der Patientenkohorte war die Frequenz von CFTR Genmutationen 11,2%. In der Subgruppe von Patienten mit idiopatischer definitiv chronischer Pankreatitis waren 12,7% der Patienten heterozygot für eine Mutation im CFTR Gen. Im Vergleich dazu ergab die Subgruppenanalyse, dass bei Patienten mit akuter Pankreatits 10% und bei Patienten mir 'possible chronic' Pancreatitis nach JPS Kriterien 9,1% Mutationen im CFTR Gen hatten. SCHLUSSFOLGERUNG: CFTR Genmutationen könnten in der Pathogenese der chronischen Pankreatitis eine Rolle spielen, weil die beobachtete Frequenz bei Patienten mit 'definitive chronic pancreatitis' am höchsten war. Bei den meisten Patienten finden sich jedoch mehrfache Risikofaktoren nach TIGAR-O, weshalb die Mutationsanalyse des CFTR-Gens nur begrenzte Bedeutung für das Management der chronischen Pankreatitis hat.

Summary

BACKGROUND/AIMS: Mutations in the gene encoding the cystic fibrosis transmembrane regulator (CFTR) are over-represented in patients with chronic pancreatitis: 13–37% of pancreatitis patients are heterozygous for CFTR mutations, compared with the carrier estimate of 3.2% in the central European population. The aim of the current study was to investigate the association between clinical manifestations of pancreatitis and CFTR carrier status. METHODS: A cohort of 133 pancreatitis patients was recruited in a confined geographical region (Tyrol – Western Austria) and analysed for the 30 most common CFTR gene mutations in Europe by multiplex PCR and gene sequencing. Pancreatitis was classified as acute or chronic according to the criteria of the Japan Pancreas Society (JPS) and etiological factors included in the TIGAR-O classification, namely toxic, idiopathic, genetic, autoimmune, recurrent and obstructive causes were assessed. RESULTS: The overall frequency of CFTR mutations in the patient cohort was 11.2%. In patients classified as 'idiopathic definitive chronic pancreatitis' (JPS criteria), the frequency of mutations was 12.7%, whereas patients with 'acute pancreatitis' or 'possible chronic pancreatitis' (JPS criteria) had a frequency of CFTR mutations of 10% and 9.1%, respectively. CONCLUSION: The frequency of CFTR mutations is highest in patients with definitive chronic pancreatitis and may therefore be regarded as a risk factor for the development of CP. However, multiple etiological factors for pancreatitis are present in the majority of patients. Mutation analysis of the CFTR gene therefore appears to be of limited diagnostic and prognostic value in the management of chronic pancreatitis.

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Authors and Affiliations

  1. Department of Medicine, Clinical Division of Gastroenterology and Hepatology, Innsbruck Medical University, Austria

    Heinz Zoller, Margit Egg, Ivo Graziadei, Marc Creus & Wolfgang Vogel

  2. Department of Genetics, Molecular and Clinical Pharmacology, Division of Clinical Genetics, Innsbruck Medical University, Austria

    Andreas R. Janecke & Judith Löffler-Ragg

  3. Current address: Department of Medicine, Clinical Division of General Internal Medicine, Innsbruck Medical University, Austria

    Judith Löffler-Ragg

  4. Current address: Department of Zoology and Limnology, Technikerstrasse 25, University of Innsbruck, Austria

    Margit Egg

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  1. Heinz Zoller
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  2. Margit Egg
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  7. Wolfgang Vogel
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Correspondence to Heinz Zoller.

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Zoller, H., Egg, M., Graziadei, I. et al. CFTR gene mutations in pancreatitis: Frequency and clinical manifestations in an Austrian patient cohort. Wien Klin Wochenschr 119, 527–533 (2007). https://doi.org/10.1007/s00508-007-0849-5

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  • DOI: https://doi.org/10.1007/s00508-007-0849-5

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