Background. Keratin 8 (K8) and 18 (K18) are the major components of the intermediate filament cytoskeleton of pancreatic acinar cells and play a relevant role in pancreatic exocrine homeostasis. Transgenic mice for K8 have shown to display progressive exocrine pancreas alterations, including dysplasia, loss of acinar architecture, redifferentiation of acinar to ductal cells, inflammation, fibrosis, and substitution of exocrine tissue by adipose tissue. Aim. To investigate whether mutations in the keratin 8 gene are associated with chronic pancreatitis. Methods. Mutations in the keratin 8 gene were determined by polymerase chain reaction/restriction fragment length polymorphism in 67 chronic pancreatitis patients and 100 normal controls. Sequence analysis was performed when necessary. Results. Glycine-to-cysteine mutations at position 61 (G61C) of the keratin 8 gene were found in six patients (8.9 vs. 0%, pc <0.003, odds ratio=21.24, confidence interval=2.74-164.42); none of the controls presented the mutation. No tyrosine-to-histidine mutations at position 53 (Y53H) were detected in any subject. Conclusion. G61C mutation of the keratin 8 gene, together with other environmental factors and/or genetic factors, could predispose to chronic pancreatitis, by interfering with the normal organization of keratin filaments.

Association of keratin 8 gene mutation with chronic pancreatitis.

FRULLONI, Luca;BOVO, Paolo;CAVALLINI, Giorgio
2003

Abstract

Background. Keratin 8 (K8) and 18 (K18) are the major components of the intermediate filament cytoskeleton of pancreatic acinar cells and play a relevant role in pancreatic exocrine homeostasis. Transgenic mice for K8 have shown to display progressive exocrine pancreas alterations, including dysplasia, loss of acinar architecture, redifferentiation of acinar to ductal cells, inflammation, fibrosis, and substitution of exocrine tissue by adipose tissue. Aim. To investigate whether mutations in the keratin 8 gene are associated with chronic pancreatitis. Methods. Mutations in the keratin 8 gene were determined by polymerase chain reaction/restriction fragment length polymorphism in 67 chronic pancreatitis patients and 100 normal controls. Sequence analysis was performed when necessary. Results. Glycine-to-cysteine mutations at position 61 (G61C) of the keratin 8 gene were found in six patients (8.9 vs. 0%, pc <0.003, odds ratio=21.24, confidence interval=2.74-164.42); none of the controls presented the mutation. No tyrosine-to-histidine mutations at position 53 (Y53H) were detected in any subject. Conclusion. G61C mutation of the keratin 8 gene, together with other environmental factors and/or genetic factors, could predispose to chronic pancreatitis, by interfering with the normal organization of keratin filaments.
Chronic pancreatitis; Genetics; Keratin 8 mutations
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/302993
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