Keratin 8 sequence variants in patients with pancreatitis and pancreatic cancer.

Abstract

Keratin 8 (KRT8) is one of the major intermediate filament proteins expressed in single-layered epithelia of the gastrointestinal tract. Transgenic mice over-expressing human KRT8 display pancreatic mononuclear infiltration, interstitial fibrosis and dysplasia of acinar cells resulting in exocrine pancreatic insufficiency. These experimental data are in accordance with a recent report describing an association between KRT8 variations and chronic pancreatitis. This prompted us to investigate KRT8 polymorphisms in patients with pancreatic disorders. The KRT8 Y54H and G62C polymorphisms were assessed in a cohort of patients with acute and chronic pancreatitis of various aetiologies or pancreatic cancer originating from Austria (n=16), the Czech Republic (n=90), Germany (n=1698), Great Britain (n=36), India (n=60), Italy (n=143), the Netherlands (n=128), Romania (n=3), Spain (n=133), and Switzerland (n=129). We also studied 4,234 control subjects from these countries and 1,492 control subjects originating from Benin, Cameroon, Ethiopia, Ecuador, and Turkey. Polymorphisms were analysed by melting curve analysis with fluorescence resonance energy transfer probes. The frequency of G62C did not differ between patients with acute or chronic pancreatitis, pancreatic adenocarcinoma and control individuals. The frequency of G62C varied in European populations from 0.4 to 3.8%, showing a northwest to southeast decline. The Y54H alteration was not detected in any of the 2,436 patients. Only 3/4,580 (0.07%) European, Turkish and Indian control subjects were heterozygous for Y54H in contrast to 34/951 (3.6%) control subjects of African descent. Our data suggest that the KRT8 alterations, Y54H and G62C, do not predispose patients to the development of pancreatitis or pancreatic cancer.

• Authors: Matthias Treiber, Hans-Ulrich Schulz, Olfert Landt, Joost P H Drenth, Carlo Castellani, Francisco X Real, Nejat Akar, Rudolf W Ammann, Mario Bargetzi, Eesh Bhatia, Andrew Glenn Demaine, Cinzia Battagia, Andrew Kingsnorth, Derek O'Reilly, Kaspar Truninger, Monika Koudova, Julius Spicak, Milos Cerny, Hans-Jürgen Menzel, Pedro Moral, Pier Franco Pignatti, Maria Grazia Romanelli, Olga Rickards, Gian Franco De Stefano, Narcis Octavian Zarnescu, Gourdas Choudhuri, Sadiq S Sikora, Jan B M J Jansen, Frank Ulrich Weiss, Matthias Pietschmann, Niels Teich, Thomas M Gress, Johann Ockenga, Hartmut Schmidt, Andreas Kage, Juliane Halangk, Jonas Rosendahl, David Alexander Groneberg, Renate Nickel, Heiko Witt
• Journal: Journal of molecular medicine (Berlin, Germany) (J Mol Med (Berl)) Vol. 84 Issue 12 Pg. 1015-22 (Dec 2006) ISSN: 0946-2716 [Print] Germany
• PMID: 17039343 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• KRT8 protein, human
• Keratin-8

Topics

• Acute Disease
• Adenocarcinoma (genetics, pathology)
• Adult
• Aged
• Alleles
• Asian People (genetics)
• Black People (genetics)
• Carcinoma, Pancreatic Ductal (genetics, pathology)
• Case-Control Studies
• Chronic Disease
• Cohort Studies
• Female
• Gene Frequency
• Genetic Variation
• Geography
• Heterozygote
• Humans
• Keratin-8 (genetics)
• Male
• Middle Aged
• Pancreatic Neoplasms (genetics, pathology)
• Pancreatitis (genetics, pathology)
• Pancreatitis, Alcoholic (genetics, pathology)
• Polymorphism, Genetic
• Retrospective Studies
• White People (genetics)