Keratin 8 sequence variants in patients with pancreatitis and pancreatic cancer.
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.
Treiber
Matthias
M
Department of Hepatology and Gastroenterology, Charité, Campus Virchow-Klinikum, Universitätsmedizin Berlin, Berlin, Germany.
Schulz
Hans-Ulrich
HU
Landt
Olfert
O
Drenth
Joost P H
JP
Castellani
Carlo
C
Real
Francisco X
FX
Akar
Nejat
N
Ammann
Rudolf W
RW
Bargetzi
Mario
M
Bhatia
Eesh
E
Demaine
Andrew Glenn
AG
Battagia
Cinzia
C
Kingsnorth
Andrew
A
O'Reilly
Derek
D
Truninger
Kaspar
K
Koudova
Monika
M
Spicak
Julius
J
Cerny
Milos
M
Menzel
Hans-Jürgen
HJ
Moral
Pedro
P
Pignatti
Pier Franco
PF
Romanelli
Maria Grazia
MG
Rickards
Olga
O
De Stefano
Gian Franco
GF
Zarnescu
Narcis Octavian
NO
Choudhuri
Gourdas
G
Sikora
Sadiq S
SS
Jansen
Jan B M J
JB
Weiss
Frank Ulrich
FU
Pietschmann
Matthias
M
Teich
Niels
N
Gress
Thomas M
TM
Ockenga
Johann
J
Schmidt
Hartmut
H
Kage
Andreas
A
Halangk
Juliane
J
Rosendahl
Jonas
J
Groneberg
David Alexander
DA
Nickel
Renate
R
Witt
Heiko
H
D000208:Acute Disease; D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D002908:Chronic Disease; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005843:Geography; D006579:Heterozygote; D006801:Humans; D053533:Keratin-8 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D010195:Pancreatitis / Q000235:genetics* / Q000473:pathology; D019512:Pancreatitis, Alcoholic / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D044465:White People / Q000235:genetics
C426203:KRT8 protein, human; D053533:Keratin-8