Keratin 8 sequence variants in patients with pancreatitis and pancreatic cancer

Treiber, Matthias; Schulz, Hans-Ulrich; Landt, Olfert; Drenth, Joost P H; Castellani, Carlo; Real, Francisco X; Akar, Nejat; Ammann, Rudolf W; Bargetzi, Mario; Bhatia, Eesh; Demaine, Andrew Glenn; Battagia, Cinzia; Kingsnorth, Andrew; O'Reilly, Derek; Truninger, Kaspar; Koudova, Monika; Spicak, Julius; Cerny, Milos; Menzel, Hans-Jürgen; Moral, Pedro; ... (2006). Keratin 8 sequence variants in patients with pancreatitis and pancreatic cancer. Journal of molecular medicine JMM, 84(12), pp. 1015-22. Berlin: Springer 10.1007/s00109-006-0096-7

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Gastroenterology

UniBE Contributor:

Truninger, Kaspar

ISSN:

0946-2716

ISBN:

17039343

Publisher:

Springer

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:50

Last Modified:

17 Mar 2015 21:52

Publisher DOI:

10.1007/s00109-006-0096-7

PubMed ID:

17039343

Web of Science ID:

000243525900005

URI:

https://boris.unibe.ch/id/eprint/20879 (FactScience: 4673)

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