title: Hemochromatosis (HFE) and transferrin receptor-1 (TFRC1) genes in sporadic porphyria cutanea tarda (sPCT).
abstract: Porphyria cutanea tarda (PCT), a disorder characterized by a photosensitive dermatosis and hepatic siderosis, is caused by a decreased activity of the hepatic enzyme uroporphyrinogen decarboxylase (UROD). Two forms of PCT have been described: a familial one (fPCT) with an inherited decrease of UROD activity in all tissues and a sporadic one (sPCT) with a decreased UROD activity restricted to the liver. Iron overload and acquired factors including hepatic viral infections, alcohol, drugs contribute to the expression of PCT. In 65 French sPCT patients and 108 controls we have evaluated the respective role of iron and HCV status, the hemochromatosis (HFE) gene mutations frequencies (H63D. S65C, C282Y), and in a case control study we searched for an association between sPCT and the human transferrin receptor-1 (TFRC1) gene whose product is thought to be in functional association with the HFE protein: three single nucleotide polymorphisms (SNPs) previously characterized and 2 novel ones were studied. The iron-related parameters and transaminases were higher in sPCT patients than those of non-porphyric controls. Of the sPCT patients studied, 28% were HCV positive. In the HFE gene, 17% of sPCT patients carried C282Y mutation compared to 4% in controls, no significant differences were found with H63D and S65C variants. Compound heterozygous genotypes, C282Y/H63D or C282Y/S65C, were not significantly different in sPCT and control groups. Independently from HFE gene mutations, an association was found between the IVS4+198 T allele in the TFRC1 gene and sPCT patients. Analysis of HFE genotypes indicated that C282Y (but not H63D nor S65C) is a susceptibility factor for the development of sPCT in West European continental patients. However, analysis of TFRC1 genotypes suggest that sPCT should be considered as a multifactorial disorder in which other intracellular iron metabolism genes could be involved.
authors.affiliation: Centre Français des Porphyries, INSERM U409, Service de Biochimie, Hĵpital Louis Mourier, Colombes, France.
authors.forename: Jérĵme
authors.initials: J
authors.lastname: Lamoril
authors.forename: Christophe
authors.initials: C
authors.lastname: Andant
authors.forename: Laurent
authors.initials: L
authors.lastname: Gouya
authors.forename: Eva
authors.initials: E
authors.lastname: Malonova
authors.forename: Bernard
authors.initials: B
authors.lastname: Grandchamp
authors.forename: Pavel
authors.initials: P
authors.lastname: Martásek
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Deybac
authors.forename: Hervé
authors.initials: H
authors.lastname: Puy
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005602:France / Q000453:epidemiology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006432:Hemochromatosis / Q000235:genetics*; D016174:Hepacivirus / Q000235:genetics; D006801:Humans; D007501:Iron / Q000097:blood; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017119:Porphyria Cutanea Tarda / Q000453:epidemiology / Q000235:genetics*; D012367:RNA, Viral / Q000097:blood; D011990:Receptors, Transferrin / Q000235:genetics*
chemical_list: D012367:RNA, Viral; D011990:Receptors, Transferrin; D007501:Iron