HFE mutations and transferrin receptor polymorphism analysis in porphyria cutanea tarda: a prospective study of 36 cases from southern France

Background Porphyria cutanea tarda (PCT) is associated in most cases with i ron overload, which may participate in decreased activity of uroporphyrinog en decarboxylase in the liver. The aetiology of this iron overload remains unknown; however, it has been demonstrated that mutations of HFE, the genet ic haemochromatosis gene, might be present in a significant proportion of A nglo-Saxon and Italian patients. Furthermore, transferrin receptor polymorp hism may influence the affinity of this receptor to its ligand with a subse quent increase of cellular iron absorption and storage. Objectives To evaluate the incidence and spectrum of HFE mutations and the relative frequency of the two main alleles of transferrin receptor in patie nts with PCT originating from southern France, and to evaluate the relation ship of these genetic data with iron status, and with hepatitis B and C and human immunodeficiency virus (HIV) infections, Methods Thirty-six consecutive patients with either sporadic or familial PC T were prospectively included between 1997 and 2000. Search for the presenc e of the three main mutations of the HFE gene and identification of the tra nsferrin receptor alleles were performed using polymerase chain reaction fo llowed by enzymatic digestion. Iron parameters and viral status for hepatit is B and C viruses and HIV were determined. Results Seven patients (19%) showed heterozygous C282Y mutation, but no C28 2Y homozygote was present; five patients (14%) carried homozygous H63D muta tion, while eight (22%) were heterozygous for this mutation, One patient wa s heterozygous for the S65C mutation (3%). Iron parameters demonstrated ove rload in all patients, without a clear difference between patients with and without deleterious mutations of the HFE gene. Infection by hepatitis C vi rus was documented in 20 patients (56%), and was significantly less frequen t in patients with deleterious HFE mutations. The profile of transferrin re ceptor alleles in PCT patients did not show significant variation compared with the general population. Conclusions This study confirms the high frequency of HFE mutations in pati ents with PCT and supports the hypothesis that HFE gene abnormalities might play a significant part in the PCT pathomechanism, probably through iron o verload; by contrast, transferrin receptor polymorphisms do not appear to p lay a significant part in iron overload in PCT.