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HFE mutations and transferrin receptor polymorphism analysis in porphyria cutanea tarda: a prospective study of 36 cases from southern France.
Br J Dermatol. 2001 Mar; 144(3):533-9.BJ

Abstract

BACKGROUND

Porphyria cutanea tarda (PCT) is associated in most cases with iron overload, which may participate in decreased activity of uroporphyrinogen decarboxylase in the liver. The aetiology of this iron overload remains unknown; however, it has been demonstrated that mutations of HFE, the genetic haemochromatosis gene, might be present in a significant proportion of Anglo-Saxon and Italian patients. Furthermore, transferrin receptor polymorphism may influence the affinity of this receptor to its ligand with a subsequent 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 patients with PCT originating from southern France, and to evaluate the relationship 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 PCT were prospectively included between 1997 and 2000. Search for the presence of the three main mutations of the HFE gene and identification of the transferrin receptor alleles were performed using polymerase chain reaction followed by enzymatic digestion. Iron parameters and viral status for hepatitis B and C viruses and HIV were determined.

RESULTS

Seven patients (19%) showed heterozygous C282Y mutation, but no C282Y homozygote was present; five patients (14%) carried homozygous H63D mutation, while eight (22%) were heterozygous for this mutation. One patient was heterozygous for the S65C mutation (3%). Iron parameters demonstrated overload in all patients, without a clear difference between patients with and without deleterious mutations of the HFE gene. Infection by hepatitis C virus was documented in 20 patients (56%), and was significantly less frequent in patients with deleterious HFE mutations. The profile of transferrin receptor 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 patients with PCT and supports the hypothesis that HFE gene abnormalities might play a significant part in the PCT pathomechanism, probably through iron overload; by contrast, transferrin receptor polymorphisms do not appear to play a significant part in iron overload in PCT.

Authors+Show Affiliations

Department of Dermatology-Phlebology, University Hospital of Montpellier, Hôpital Saint-Eloi, 80 avenue Augustin Fliche, 34295 Montpellier cedex 5, France. ofdereure@wanadoo.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11260010

Citation

Dereure, O, et al. "HFE Mutations and Transferrin Receptor Polymorphism Analysis in Porphyria Cutanea Tarda: a Prospective Study of 36 Cases From Southern France." The British Journal of Dermatology, vol. 144, no. 3, 2001, pp. 533-9.
Dereure O, Aguilar-Martinez P, Bessis D, et al. HFE mutations and transferrin receptor polymorphism analysis in porphyria cutanea tarda: a prospective study of 36 cases from southern France. Br J Dermatol. 2001;144(3):533-9.
Dereure, O., Aguilar-Martinez, P., Bessis, D., Perney, P., Vallat, C., Guillot, B., Blanc, F., & Guilhou, J. J. (2001). HFE mutations and transferrin receptor polymorphism analysis in porphyria cutanea tarda: a prospective study of 36 cases from southern France. The British Journal of Dermatology, 144(3), 533-9.
Dereure O, et al. HFE Mutations and Transferrin Receptor Polymorphism Analysis in Porphyria Cutanea Tarda: a Prospective Study of 36 Cases From Southern France. Br J Dermatol. 2001;144(3):533-9. PubMed PMID: 11260010.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - HFE mutations and transferrin receptor polymorphism analysis in porphyria cutanea tarda: a prospective study of 36 cases from southern France. AU - Dereure,O, AU - Aguilar-Martinez,P, AU - Bessis,D, AU - Perney,P, AU - Vallat,C, AU - Guillot,B, AU - Blanc,F, AU - Guilhou,J J, PY - 2001/3/22/pubmed PY - 2001/7/13/medline PY - 2001/3/22/entrez SP - 533 EP - 9 JF - The British journal of dermatology JO - Br. J. Dermatol. VL - 144 IS - 3 N2 - BACKGROUND: Porphyria cutanea tarda (PCT) is associated in most cases with iron overload, which may participate in decreased activity of uroporphyrinogen decarboxylase in the liver. The aetiology of this iron overload remains unknown; however, it has been demonstrated that mutations of HFE, the genetic haemochromatosis gene, might be present in a significant proportion of Anglo-Saxon and Italian patients. Furthermore, transferrin receptor polymorphism may influence the affinity of this receptor to its ligand with a subsequent 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 patients with PCT originating from southern France, and to evaluate the relationship 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 PCT were prospectively included between 1997 and 2000. Search for the presence of the three main mutations of the HFE gene and identification of the transferrin receptor alleles were performed using polymerase chain reaction followed by enzymatic digestion. Iron parameters and viral status for hepatitis B and C viruses and HIV were determined. RESULTS: Seven patients (19%) showed heterozygous C282Y mutation, but no C282Y homozygote was present; five patients (14%) carried homozygous H63D mutation, while eight (22%) were heterozygous for this mutation. One patient was heterozygous for the S65C mutation (3%). Iron parameters demonstrated overload in all patients, without a clear difference between patients with and without deleterious mutations of the HFE gene. Infection by hepatitis C virus was documented in 20 patients (56%), and was significantly less frequent in patients with deleterious HFE mutations. The profile of transferrin receptor 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 patients with PCT and supports the hypothesis that HFE gene abnormalities might play a significant part in the PCT pathomechanism, probably through iron overload; by contrast, transferrin receptor polymorphisms do not appear to play a significant part in iron overload in PCT. SN - 0007-0963 UR - https://www.unboundmedicine.com/medline/citation/11260010/HFE_mutations_and_transferrin_receptor_polymorphism_analysis_in_porphyria_cutanea_tarda:_a_prospective_study_of_36_cases_from_southern_France_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0007-0963&date=2001&volume=144&issue=3&spage=533 DB - PRIME DP - Unbound Medicine ER -