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Blood, Vol. 95 No. 5 (March 1), 2000:
pp. 1565-1571
Hemochromatosis genes and other factors contributing to the
pathogenesis of porphyria cutanea tarda
Zaneta J. Bulaj,
John D. Phillips,
Richard S. Ajioka,
Michael R. Franklin,
Linda M. Griffen,
Donald J. Guinee,
Corwin Q. Edwards, and
James P. Kushner
From the Departments of Medicine, Pharmacology, and
Pathology, the University of Utah School of Medicine, and the Latter
Day Saints Hospital, Salt Lake City, UT.
Inherited and acquired factors have been implicated in the
pathogenesis of porphyria cutanea tarda (PCT), a disorder characterized by a photosensitive dermatosis and hepatic siderosis. This study, comprising 108 patients with PCT, was intended to define the role of
hemochromatosis gene (HFE) mutations in the expression of PCT and to determine the contribution of acquired factors including alcohol, hepatitis C virus (HCV), and estrogen. The 2 known HFE mutations, cysteine 282 tyrosine (Cys282Tyr)
and histidine 63 asparagine (His63Asp), were detected by
polymerase chain reaction, and anti-HCV immunoglobulin G was detected
serologically. Liver biopsies were graded for iron content,
inflammation, and fibrosis. Estimates of alcohol and estrogen use were
based on a questionnaire. Of the PCT patients tested, 19% were
homozygous for the Cys282Tyr mutation; controls were equal to
0.5%. The compound heterozygous genotype was detected in 7% of the
PCT patients; controls were less than 1%. The transferrin saturation,
serum ferritin, and liver iron burden of all PCT patients were higher
than those of nonporphyric controls. The highest values were found in
PCT patients homozygous for the Cys282Tyr mutation. Of the
patients studied, 59% were HCV positive (compared with 1.8% of the
population), and 46% consumed more than 70 g of alcohol daily. Of the
female patients, 63% were ingesting estrogens. Hepatic damage was most marked in patients with the Cys282Tyr/Cys282Tyr genotype who
had HCV and drank heavily. Homozygosity for the Cys282Tyr
mutation and HCV are the greatest risk factors for expression of PCT,
and in most patients, more than 1 risk factor was identified. It was common for patients with HCV to consume alcohol. Patients with PCT
should be screened for HFE mutations and for HCV.
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