title: Smoking but not homozygosity for CYP1A2 g-163A allelic variant leads to earlier disease onset in patients with sporadic porphyria cutanea tarda.
abstract: Porphyria cutanea tarda (PCT) results from decreased activity of hepatic uroporphyrinogen decarboxylase (UROD). Both sporadic and familial forms are characterised by typical cutaneous lesions triggered by genetic/environmental factors. Studies in rodents showed that cytochrome P4501A2 (CYP1A2) plays a central role in the synthesis of a competitive inhibitor of hepatic UROD, but there is little evidence in humans. The impact of smoking and CYP1A2 g-163C > A allelic variant upon first appearance of clinical signs was investigated in 102 patients (80 sporadic-PCT) and 150 healthy donors from Spain. We found an increase in the frequency of CYP1A2 g-163A allele in patients with PCT when compared with controls, although the more inducible A/A genotype had no effect on the onset age. In sporadic-PCT, smoking leads to earlier onset of clinically overt disease in moderate-to-heavy smokers (>or=10 cigarettes/day). In conclusion, this study provides evidence that smoking hastens the onset of cutaneous symptoms in sporadic-PCT patients.
authors.forename: Antonio
authors.initials: A
authors.lastname: Fontanellas
authors.forename: María
authors.initials: M
authors.lastname: Martínez-Fresno
authors.forename: María Concepción
authors.initials: MC
authors.lastname: Garrido-Astray
authors.forename: Teresa
authors.initials: T
authors.lastname: Perucho
authors.forename: María-Josefa
authors.initials: MJ
authors.lastname: Morán-Jiménez
authors.forename: María
authors.initials: M
authors.lastname: García-Bravo
authors.forename: Manuel
authors.initials: M
authors.lastname: Méndez
authors.forename: Pamela
authors.initials: P
authors.lastname: Poblete-Gutiérrez
authors.forename: Jorge
authors.initials: J
authors.lastname: Frank
authors.forename: Nuno
authors.initials: N
authors.lastname: Henriques-Gil
authors.forename: Rafael Enríquez
authors.initials: RE
authors.lastname: de Salamanca
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008875:Middle Aged; D017119:Porphyria Cutanea Tarda / Q000208:ethnology / Q000209:etiology / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects*; D013030:Spain
chemical_list: C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2