TY - JOUR
T1 - Smoking but not homozygosity for CYP1A2 g-163A allelic variant leads to earlier disease onset in patients with sporadic porphyria cutanea tarda
AU - Fontanellas, Antonio
AU - Martinez-Fresno, Maria
AU - Concepcion Garrido-Astray, Maria
AU - Perucho, Teresa
AU - Moran-Jimenez, Maria-Josefa
AU - Garcia-Bravo, Maria
AU - Mendez, Manuel
AU - Poblete-Gutierrez, Pamela
AU - Frank, Jorge
AU - Henriques-Gil, Nuno
AU - Enriquez de Salamanca, Rafael
PY - 2010/8
Y1 - 2010/8
N2 - 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 (>= 10 cigarettes/day). In conclusion, this study provides evidence that smoking hastens the onset of cutaneous symptoms in sporadic-PCT patients.
AB - 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 (>= 10 cigarettes/day). In conclusion, this study provides evidence that smoking hastens the onset of cutaneous symptoms in sporadic-PCT patients.
KW - cytochrome P4501A2 allelic variant
KW - onset of cutaneous symptoms
KW - porphyria
KW - tobacco smoke
KW - uroporphyrinogen decarboxylase
U2 - 10.1111/j.1600-0625.2009.01040.x
DO - 10.1111/j.1600-0625.2009.01040.x
M3 - Article
C2 - 20163457
SN - 0906-6705
VL - 19
SP - E326-E328
JO - Experimental Dermatology
JF - Experimental Dermatology
IS - 8
ER -