HFE genotypes in patients with chronic pancreatitis and pancreatic adenocarcinoma.
OBJECTIVE
The homozygous p.C282Y variant of the HFE gene is a major risk factor for hereditary hemochromatosis, a disorder of iron metabolism resulting in progressive iron accumulation in a variety of organs including the pancreas. Heterozygosity of p.C282Y and p.H63D may increase susceptibility to chronic liver and pancreatic disease. This study determines the frequencies of p.C282Y and p.H63D alterations in patients with chronic pancreatitis and pancreatic adenocarcinoma.


METHODS
In total, 958 patients (349 with alcoholic pancreatitis, 343 with idiopathic pancreatitis, 64 with familial chronic pancreatitis, 34 with acute pancreatitis, and 168 with pancreatic adenocarcinoma) were enrolled and compared with 681 healthy and 100 alcoholic controls. Furthermore, 45 parent-offspring trios were included for segregation analysis. Genotyping of p.C282Y and p.H63D was performed by restriction fragment length polymorphism or melting curve analyses.


RESULTS
No significant differences were found in heterozygosity for p.C282Y and p.H63D when patients with alcoholic (8.0/21.5%), idiopathic (7.3/24.5%), or familial (9.8/23.0%) pancreatitis, or pancreatic adenocarcinoma (5.4/28.6%) were compared with healthy (6.2/24.8%) and alcoholic (7.0/25.0%) controls. Neither genotype was associated with the presence of secondary diabetes mellitus in patients with chronic pancreatitis.


CONCLUSIONS
Although hemochromatosis is associated with pancreatic pathology, the p.C282Y and p.H63D variants do not play a significant role in the pathogenesis of chronic pancreatitis or pancreatic adenocarcinoma.
Hucl
Tomas
T
Department of Medicine II, University of Heidelberg, Mannheim, Germany.
Kylanpää-Bäck
Marja-Leena
ML
Witt
Heiko
H
Künzli
Beat
B
Lempinen
Marko
M
Schneider
Alexander
A
Kemppainen
Esko
E
Löhr
Matthias
M
Friess
Helmut
H
Ockenga
Johann
J
Rosendahl
Jonas
J
Schulz
Hans-Ulrich
HU
Gress
Thomas
T
Singer
Manfred V
MV
Pfützer
Roland H
RH
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D006432:Hemochromatosis / Q000235:genetics / Q000473:pathology; D000071020:Hemochromatosis Protein; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D019512:Pancreatitis, Alcoholic / Q000235:genetics / Q000473:pathology; D050500:Pancreatitis, Chronic / Q000235:genetics* / Q000473:pathology; D012150:Polymorphism, Restriction Fragment Length
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins