Smoking but not homozygosity for CYP1A2 g-163A allelic variant leads to earlier disease onset in patients with sporadic porphyria cutanea tarda.
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.
Fontanellas
Antonio
A
Martínez-Fresno
María
M
Garrido-Astray
María Concepción
MC
Perucho
Teresa
T
Morán-Jiménez
María-Josefa
MJ
García-Bravo
María
M
Méndez
Manuel
M
Poblete-Gutiérrez
Pamela
P
Frank
Jorge
J
Henriques-Gil
Nuno
N
de Salamanca
Rafael Enríquez
RE
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
C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2