FREQUENCY OF INTRON 1 C/A POLYMORPHISM OF THE CYP1A2 IN SPANISH PATIENTS WITH PORPHYRIA CUTANEA TARDA

María Martínez-Fresno (1), Nuno Henriques-Gil (1), María-Concepción Garrido (2), Teresa Perucho-Alcalde (1), María García-Bravo (2), Manuel Méndez (2), Antonio Fontanellas (2), Rafael Enríquez de Salamanca (2)

(1) Lab. Genética, Universidad San Pablo-CEU, Montepríncipe, Madrid, Spain. (2) Centro de Investigación. Hospital 12 de Octubre, Madrid, Spain

Porphyria cutanea tarda (PCT) is characterized by partial deficient activity of the hepatic uroporphyrinogen decarboxylase enzyme (UROD). The enzymatic defect of the UROD alone is not sufficient to provoke clinical symptoms of PCT. An increased frequency of the highly inducible A/A genotype of cytochrome CYP1A2 has been described in patients with PCT and inheritance of this genotype was suggested as a susceptibility factor in development of overt-PCT.

The aim of this study was to determine the frequency of the CYP1A2 C/A polymorphism in intron 1 in a series of 110 patients with PCT and in 146 normal subjects from Spain. Patients were divided into familial-PCT, which are associated with mutations in the UROD gene and decrease erythrocyte UROD activity, and sporadic-PCT who exhibited normal UROD activity in erythrocytes. The rare familial occurrence of sporadic-PCT cases were classified as Type III-PCT. CYP1A2 genotype was determined after PCR amplification plus ApaI restriction enzyme digestion. No differences were found between the three PCT groups. Among the PCT patients 4 were C/C homozygous while 57 were C/A heterozygous and 49 A/A homozygous. The comparison with the control population (18 C/C, 68 C/A, and 60 A/A) revealed statistical differences (contingency c2=6.044; 2 d.f.; p<0.05). This supports the idea that the “A” allele could be a susceptibility factor in the development of PCT.