Comprehensive cytochrome P450 CYP1A2 gene analysis in French caucasian patients with familial and sporadic porphyria cutanea tarda

Br J Dermatol. 2012 Feb;166(2):425-9. doi: 10.1111/j.1365-2133.2011.10642.x. Epub 2011 Dec 14.

Abstract

Background: Porphyria cutanea tarda (PCT), the most frequent type of porphyria, results from decreased uroporphyrinogen decarboxylase (UROD) activity. Two forms of PCT have been described: a familial form (fPCT) characterized by the inherited decrease of UROD activity in all tissues and a sporadic form (sPCT) characterized by decreased UROD activity in the liver. Cytochrome P450 CYP1A2 plays a major role in triggering experimental uroporphyria in rodents. It has been suggested that the highly inducible -163A/A genotype of the CYP1A2 gene could confer a heightened risk of PCT in patients.

Objectives: To examine the impact of CYP1A2 polymorphisms on the clinical course of PCT.

Methods: We performed an extensive CYP1A2 gene analysis in 96 (48 fPCT and 48 sPCT) unrelated French caucasian patients with PCT and in 99 healthy volunteers of similar ethnic origin. Results We did not observe any difference in CYP1A2 allele distribution, including a novel and rare CYP1A2 c.1063C>T (p.R355W) single nucleotide polymorphism. In addition, we compared the frequency of the -163A highly inducible allele both in patients with symptomatic fPCT (n = 48) and in asymptomatic UROD gene mutations carrier relatives (n=54). This variant was not over-represented in patients with PCT vs. either healthy volunteers or asymptomatic UROD gene mutation carriers.

Conclusions: The CYP1A2 genotype does not appear to be a major susceptibility factor in the development of fPCT or sPCT in the French population.

MeSH terms

  • Case-Control Studies
  • Cytochrome P-450 CYP1A2 / genetics*
  • France
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • Heterozygote
  • Humans
  • Mutation / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Porphyria Cutanea Tarda / genetics*
  • White People / genetics*

Substances

  • Cytochrome P-450 CYP1A2