Cytochrome P450 Isoenzimes Single Nucleotide Polymorphysms (SNPs) are Really Involved in Porphyria Cutanea Tarda Development ?

DIEGO MIGUEL GORDILLO; LUBNA ABOU ASSALI; GABRIELA NORA CERBINO; ALCIRA MARÍA DEL CARMEN BATLLE; VICTORIA ESTELA PARERA; MARÍA VICTORIA ROSSETTI

BORDEAUX

Congreso; INTERNATINAL CONGRESS ON PORPHYRINS AND PORPHYRIAS; 2017

It was suggested a role for some CYP1A1 and CYP1A2 isoformes in PCT development but the results from different populations are controversial. We analised three polymorphisims, one in CYP1A2 and two in CYP1A1 in a group of Argentinean PCT patients and in a control group. One hundred PCT patients, 37 H-PCT and 63 A-PCT were analysed employing PCR-RFLP 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 (-163 AC) 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) genotypes vs C/C genotype and also A allele vs C alelle (p=0,042) for total PCT vs control group. For CYP1A1*4A or m4 (c.4887 CA; p.T461N), C alelle and C/C genotype are the most frequent in each group. A significant differece for C/C and C/A genotypes vs A/A genotype were found (p=0.028 and C/A p=0.014 respectively). The same tendency was observed for PCT-H vs Control and A-PCT. For CYP1A1*2C or m2 (c.4889 AG; p.I462V), A/A genotype and A alelle frequencies were higher for all groups. In this case G alelle codified for a higher activity enzyme than wild type allele. Significant differences were found only for A-PCT vs control for A/A vs A/G genotypes (p=0.016). So we could concluded that these polymorphisms could be, among others, a risk factor to PCT clinical signs triggering in Argentinean population.