TY - JOUR
T1 - HFE genotypes in patients with chronic pancreatitis and pancreatic adenocarcinoma
AU - Hucl, Tomas
AU - Kylanpää-Bäck, Marja Leena
AU - Witt, Heiko
AU - Künzli, Beat
AU - Lempinen, Marko
AU - Schneider, Alexander
AU - Kemppainen, Esko
AU - Löhr, Matthias
AU - Friess, Helmut
AU - Ockenga, Johann
AU - Rosendahl, Jonas
AU - Schulz, Hans Ulrich
AU - Gress, Thomas
AU - Singer, Manfred V.
AU - Pfützer, Roland H.
PY - 2007/7
Y1 - 2007/7
N2 - PURPOSE: 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. CONCLUSION: 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.
AB - PURPOSE: 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. CONCLUSION: 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.
KW - Chronic pancreatitis
KW - Genetic analysis
KW - HFE
KW - Hemochromatosis
KW - Pancreatic adenocarcinoma
UR - http://www.scopus.com/inward/record.url?scp=34547702300&partnerID=8YFLogxK
U2 - 10.1097/GIM.0b013e3180986df4
DO - 10.1097/GIM.0b013e3180986df4
M3 - Article
C2 - 17666895
AN - SCOPUS:34547702300
SN - 1098-3600
VL - 9
SP - 479
EP - 483
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 7
ER -
