The role of cytochrome P450 isoenzymes on Porphyria Cutanea Tarda development

GORDILLO DIEGO MIGUEL; ABOU ASSALY LUBNA; CERBINO GABRIELA; VARELA LAURA; BATLLE, ALCIRA; PARERA VICTORIA ESTELA; ROSSETTI MARÍA VICTORIA

Mar del Plata, Buenos Aires - Argentina

Congreso; LXI REUNION CIENTIFICA ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACION CLINICA (SAIC).; 2016

Sociedad Argentina de Investigación Clínica

Porphyria Cutanea Tarda (PCT) is a disorder characterized by a reduction of Uroporphyrinogen decarboxilase (UROD) activity in all tissues or only in liver in hereditary (H-PCT or acdquired (A-PCT) PCT forms, respectively. In both PCT types multiple susceptibility factors, such as iron excess, smoking, estrogens and halogenated polycyclic hydrocarbons, contribute to liver UROD deficiency. It was suggested a role for CYP1A1 and CYP1A2 isoformes in PCT development. We analised three polymorphisims, one in CYP1A2 and two in CYP1A1 in a group of Argentinean PCT patients and in a control group, with the aim of investigating if they could play some role on PCT manifestation. One hundred PCT patients, 37 H-PCT and 63 A-PCT employing PCR-RFLP were analysed and each variant was compared with 73 controls. The Fisher exact test was used to detect differences in alelles and genotype frequencies, odds ratio and 95% confidential interval. For CYP1A2*1F (-734 CA) the frecuences of A alelle and A/A genotype are higher for both types of PCT vs control group, being the A allele associated to a more transcriptional activity of CYP1A2 gene. There are significant diferences for A/A (p0.022) and A/C (p0.022) vs C/C genotype and also A allele vs C alelle (p0.018) for total PCT vs control group. For CYP1A1*4A (c.4487 CA), C alelle and C/C genotype are the most frequent for total PCT vs control group. A significant differece for A/A genotype vs C/C genotype (p0.028) and C/A (p0.014) was found. The same was observed in H-PCT vs control group, p0.0001 and p0.0005, respectively. For CYP 1A1 *2C (c.4889 AG), A/A genotype and A alelle frequencies were higher for all groups. In this case G alelle codified for a more activity enzyme. Significant difference were found only for A-PCT vs control for A/A vs A/G genotypes (p0.0016). So we could concluded that these polymorphisms could be, among others, a risk factor to PCT clinical signs triggering in Argentinean population.