The Frequency of Hemochromatosis–Associated Alleles Is Increased in British Patients With Sporadic Porphyria Cutanea Tarda

Abstract

of the hemochromatosis-linked HLA allele, HLA-A3, and The cause of the hepatic siderosis and iron overload PCT 7-9 but not by others. [10][11][12][13] Recently it has been shown that that is common in porphyria cutanea tarda (PCT) is unthe hemochromatosis gene (HFE) is most likely located close certain. Heterozygosity for genetic hemochromatosis to the microsatellite DNA marker, D6S1260 (formerly CS5), has been supported by some studies of the association which is 700kb telomeric to the marker D6S105, which is between the HLA-A3 antigen and porphyria cutanea itself 2-3 cm telomeric to the HLA-A locus. The cause of the hepatic siderosis and mild iron overload a denaturing gel.14 For D6S1260 one primer was labelled with [g-that is common in PCT is uncertain. The hypothesis that it 32 P]adenosine triphosphate using T4 polynucleotide kinase; the polyis caused by heterozygosity for genetic hemochromatosis merase chain reaction products were denatured, fractionated by elec-(GH) 7 has been supported by some studies of the association trophoresis in polyacrylamide gels under denaturing conditions, and visualised by autoradiography.14 Statistical Analysis. Allele frequencies were determined by direct counting and individuals possessing a single allele were assumed to Abbreviations: PCT, porphyria cutanea tarda; GH, genetic hemochromatosis; HFE, hebe homozygous for that allele. The significance of differences between Other Methods. Transferrin saturation was calculated from the Received May 15, 1996; accepted August 29, 1996. concentrations of plasma iron, measured by atomic absorption spec-

C282Y and H63D mutations in the HFE gene are not associated with porphyria cutanea tarda in bulgaria

“…This is in contrast to reports of populations of European descent, including Britains, Dutchmen, Americans, Australians, and South Africans. [8][9][10][11][12][13] However, our findings are in accordance with reports from the Italian population recently published by Sampietro et al 6 who also found no association between the C282Y mutation and SPCT. The H63D mutation was observed in 10 of the 48 PCT patients corresponding to 20.8%.…”

Heterozygosity for hereditary hemochromatosis is associated with more fibrosis in chronic hepatitis C

“…19 The C282Y mutation, which is found in 6% to 11% of the U.K. population, 18,20 is in complete linkage disequilibrium with the H63D mutation. The H63D mutation is found in 16% to 25% of the population, 21 but its role, if any in HH, is controversial. It seems to be associated with hemochromatosis only when inherited together with the C282Y mutation.…”

Hepatic uroporphyrinogen decarboxylase activity in porphyria cutanea tarda patients: The influence of virus C infection

“…A liver-specific process that causes clinically overt PCT in response to hepatitis viral infection might be caused by interactions between genes that control the level of URO-D in the cells and genes of which the expression induces the inactivation of the protein. In this manner, Roberts et al 30,33 have shown that hemochromatosisassociated alleles were more frequently carried by British patients with s-PCT than by the general population. Different alleles of other modulatory genes of URO-D could be related to a more or less pronounced sensitivity to viral infection in s-PCT patients.…”

“…Iron participates in the generation of reactive oxygen species and in the oxidation of uroporphyrinogen to uroporphyrin, 28,29 contributing to the development of the hepatic lesions. A recent study reveals that inheritance of one or more hemochromatosis mutant alleles is an important susceptibility factor for the development of s-PCT [30][31][32][33] in some countries.…”