THE C282Y MUTATION IN THE HEMOCHROMATOSIS GENE (HFE) AND HEPATITIS-C VIRUS-INFECTION ARE INDEPENDENT COFACTORS FOR PORPHYRIA-CUTANEA-TARDA IN AUSTRALIAN PATIENTS

Background/Aim: Whether mutations in the putative haemochromatosis gen e (HFE) and hepatitis C virus act independently to precipitate porphyr ia cutanea tarda is unknown, The aim of the study was to investigate t he relationship between mutations in HFE, hepatitis C and porphyria cu tanea tarda, Methods: The frequencies of the C282Y and H63D mutations in HFE were determined in 27 patients with porphyria cutanea tarda and compared with the reported control frequencies, In addition, the pres ence of hepatitis C virus infection was identified and related to the patients' HFE status, Results: The C282Y mutation was found in 44.4% o f patients compared with the control frequency of 12% (p<0.001), Three patients were homozygous for the C282Y mutation, two of whom did not meet current clinical diagnostic criteria for expressed haemochromatos is. The proportion of patients with the H63D mutation did not differ f rom the reported control frequency The mean transferrin saturation and serum ferritin concentration were similar in porphyria cutanea tarda patients who were homozygous normal and heterozygous for the C282Y mut ation, but greater in both groups than previously reported in healthy controls, Seven (25.9%) patients were anti-HCV IgG positive, None of t hese patients carried the C282Y mutation, Porphyria cutanea tarda pati ents heterozygous for the C282Y mutation and patients with anti-HCV an tibodies had elevated transferrin saturations and serum ferritin conce ntrations, Conclusions: The raised frequency of the C282Y mutation in porphyria cutanea tarda indicates that this mutation is likely to be a predisposing factor, However, abnormalities of iron indices also exis t in porphyria cutanea tarda patients without mutations in HFE. Hepati tis C virus infection is likely to be another common precipitating fac tor for porphyria cutanea tarda which acts independently of the C282Y mutation.