C282Y and H63D mutation of the hemochromatosis gene in German porphyria cutanea tarda patients.
OBJECTIVE
Patients with porphyria cutanea tarda (PCT) have a susceptibility to reversible inactivation of hepatocyte uroporphyrinogen decarboxylase, which can be triggered by alcohol, hepatitis C virus, and other agents. Inherited factors that may predispose to PCT include the C282Y mutation in the hemochromatosis (HFE) gene.


METHODS
We analyzed the hemochromatosis mutations C282Y and H63D in liver biopsies and serum samples of 190 German patients (mean age 48+/-12.5 years) with sporadic PCT. The hepatic iron concentration was determined within the liver tissue. Age-matched healthy blood donors (115 donors) served as controls.


RESULTS
The C282Y and H63D mutations were found in 75 (39%) and 85 (45%) of 190 patients with PCT, respectively. Twenty-two patients (12%) were homozygous for the C282Y mutation, and eighteen patients (9%) were compound heterozygotes, displaying both the C282Y and the H63D mutation. Within the control group, 3 of 115 patients were heterozygous for C282Y (3%) and 12 for H63D (10%). Serum and hepatic iron, ferritin, transferrin saturation, or liver enzymes did not differ significantly between patients with or without HFE mutations.


CONCLUSIONS
The high frequency of homo- and heterozygosity for the C282Y and H63D alleles strongly suggests that these mutations are important predisposing factors for PCT in German patients.
Tannapfel
A
A
Institute of Pathology, University of Leipzig, Germany.
Stölzel
U
U
Köstler
E
E
Melz
S
S
Richter
M
M
Keim
V
V
Schuppan
D
D
Wittekind
C
C
D004247:DNA / Q000032:analysis; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005293:Ferritins / Q000097:blood; D005787:Gene Frequency; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006432:Hemochromatosis / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D017119:Porphyria Cutanea Tarda / Q000097:blood / Q000235:genetics*; D012016:Reference Values; D014168:Transferrin / Q000032:analysis
D017931:DNA Primers; D014168:Transferrin; D004247:DNA; D005293:Ferritins; D007501:Iron