title: Keratin 8 variants are associated with cryptogenic hepatitis.
abstract: Keratins 8 and 18 (K8 and K18) are the cytoskeletal intermediate filament proteins of adult hepatocytes. Murine models indicate that mutations in the K8- and K18-encoding genes predispose to liver injury. Moreover, studies showed an association of K8/K18 variants with human acute and chronic liver diseases. However, only little is known about a putative association of K8/K18 variants with cryptogenic hepatitis, a frequent liver disease of enigmatic etiology, often necessitating liver transplantation. Therefore, we analyzed whether K8 variants associate with cryptogenic hepatitis in a German cohort of patients in comparison to control blood bank donors. Genomic DNA isolated from liver biopsies of cryptogenic hepatitis patients or peripheral blood of healthy donors was analyzed for K8 variants by PCR amplification and direct DNA sequencing. We identified 8 novel heterozygous or homozygous amino acid-altering K8 variants in 5 of 62 cryptogenic hepatitis patients (8.1 %) and in none of 67 controls (P = 0.02). Previously described K8 variants p.G62C and p.R341H were found at similar incidence in cryptogenic hepatitis patients and controls. Hence, they were considered as polymorphisms not associated with liver disease progression. In conclusion, previously undescribed K8 variants associate with cryptogenic hepatitis in a German cohort of patients, possibly predisposing carriers to the development of liver disease.
authors.affiliation: Institute for Pathology, University Hospital of Cologne, 50924, Cologne, Germany. mario.zierden@uni-koeln.de
authors.forename: Mario
authors.initials: M
authors.lastname: Zierden
authors.forename: Arndt-Hendrik
authors.initials: AH
authors.lastname: Penner
authors.forename: Manuel
authors.initials: M
authors.lastname: Montesinos-Rongen
authors.forename: Maren
authors.initials: M
authors.lastname: Weferling
authors.forename: Uta
authors.initials: U
authors.lastname: Drebber
authors.forename: Judith
authors.initials: J
authors.lastname: Stift
authors.forename: Jochen W U
authors.initials: JW
authors.lastname: Fries
authors.forename: Margarete
authors.initials: M
authors.lastname: Odenthal
authors.forename: Stephan
authors.initials: S
authors.lastname: Rosenkranz
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Dienes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D006505:Hepatitis / Q000235:genetics* / Q000473:pathology; D006801:Humans; D053533:Keratin-8 / Q000235:genetics*; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: D053533:Keratin-8