Length of Variable Numbers of Tandem Repeats in the Carboxyl Ester Lipase (CEL) Gene May Confer Susceptibility to Alcoholic Liver Cirrhosis but Not Alcoholic Chronic Pancreatitis.
BACKGROUND
Carboxyl-ester lipase (CEL) contributes to fatty acid ethyl ester metabolism, which is implicated in alcoholic pancreatitis. The CEL gene harbours a variable number of tandem repeats (VNTR) region in exon 11. Variation in this VNTR has been linked to monogenic pancreatic disease, while conflicting results were reported for chronic pancreatitis (CP). Here, we aimed to investigate a potential association of CEL VNTR lengths with alcoholic CP.


METHODS
Overall, 395 alcoholic CP patients, 218 patients with alcoholic liver cirrhosis (ALC) serving as controls with a comparable amount of alcohol consumed, and 327 healthy controls from Germany and the United Kingdom (UK) were analysed by determination of fragment lengths by capillary electrophoresis. Allele frequencies and genotypes of different VNTR categories were compared between the groups.


RESULTS
Twelve repeats were overrepresented in UK ACP patients (P = 0.04) compared to controls, whereas twelve repeats were enriched in German ALC compared to alcoholic CP patients (P = 0.03). Frequencies of CEL VNTR lengths of 14 and 15 repeats differed between German ALC patients and healthy controls (P = 0.03 and 0.008, respectively). However, in the genotype and pooled analysis of VNTR lengths no statistical significant association was depicted. Additionally, the 16-16 genotype as well as 16 repeats were more frequent in UK ALC than in alcoholic CP patients (P = 0.034 and 0.02, respectively). In all other calculations, including pooled German and UK data, allele frequencies and genotype distributions did not differ significantly between patients and controls or between alcoholic CP and ALC.


CONCLUSIONS
We did not obtain evidence that CEL VNTR lengths are associated with alcoholic CP. However, our results suggest that CEL VNTR lengths might associate with ALC, a finding that needs to be clarified in larger cohorts.
KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway.|Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
Karianne
K
Fjeld
Department of Internal Medicine, Neurology and Dermatology, Division of Gastroenterology and Rheumatology, University of Leipzig, Leipzig, Germany.
Sebastian
S
Beer
NIHR Liverpool Pancreas Biomedical Research Unit, Royal Liverpool University Hospital, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
Marianne
M
Johnstone
Department of Internal Medicine, Neurology and Dermatology, Division of Gastroenterology and Rheumatology, University of Leipzig, Leipzig, Germany.
Constantin
C
Zimmer
Department of Internal Medicine, Neurology and Dermatology, Division of Gastroenterology and Rheumatology, University of Leipzig, Leipzig, Germany.
Joachim
J
Mössner
Department of Internal Medicine I, Martin Luther University, Halle, Germany.
Claudia
C
Ruffert
Department of Internal Medicine, Neurology and Dermatology, Division of Gastroenterology and Rheumatology, University of Leipzig, Leipzig, Germany.
Mario
M
Krehan
Department of Internal Medicine, Neurology and Dermatology, Division of Gastroenterology and Rheumatology, University of Leipzig, Leipzig, Germany.
Christian
C
Zapf
KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Pediatrics, Haukeland University Hospital, Bergen, Norway.
Pål Rasmus
PR
Njølstad
KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway.|Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
Stefan
S
Johansson
Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, German Red Cross Blood Service of Baden-Württemberg-Hessen, Mannheim, Germany.
Peter
P
Bugert
Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
Fabio
F
Miyajima
Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
Triantafillos
T
Liloglou
NIHR Liverpool Pancreas Biomedical Research Unit, Royal Liverpool University Hospital, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
Laura J
LJ
Brown
NIHR Liverpool Pancreas Biomedical Research Unit, Royal Liverpool University Hospital, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
Simon A
SA
Winn
NIHR Liverpool Pancreas Biomedical Research Unit, Royal Liverpool University Hospital, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
Kelly
K
Davies
NIHR Liverpool Pancreas Biomedical Research Unit, Royal Liverpool University Hospital, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
Diane
D
Latawiec
NIHR Birmingham Liver Biomedical Research Unit, Queen Elizabeth Hospital and University of Birmingham, Birmingham, United Kingdom.
Bridget K
BK
Gunson
Department of Cellular & Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
David N
DN
Criddle
Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
Munir
M
Pirmohamed
Department of Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Robert
R
Grützmann
Department of Internal Medicine I, Martin Luther University, Halle, Germany.
Patrick
P
Michl
NIHR Liverpool Pancreas Biomedical Research Unit, Royal Liverpool University Hospital, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
William
W
Greenhalf
KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway.|Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, Bergen, Norway.|Department of Pathology, Haukeland University Hospital, Bergen, Norway.
Anders
A
Molven
NIHR Liverpool Pancreas Biomedical Research Unit, Royal Liverpool University Hospital, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
Robert
R
Sutton
Department of Internal Medicine I, Martin Luther University, Halle, Germany.
Jonas
J
Rosendahl
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002908:Chronic Disease; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008104:Liver Cirrhosis, Alcoholic / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D019512:Pancreatitis, Alcoholic / Q000453:epidemiology / Q000235:genetics*; D006113:United Kingdom / Q000453:epidemiology
C054621:CEL protein, human; D008049:Lipase