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

GORDILLO, DIEGO; VARELA, LAURA; ROSSETTI, MARIA VICTORIA; CERBINO, GABRIELA; ABOU ASSALI, LUBNA; PARERA, VICTORIA; BATLLE, ALCIRA

Burdeos

Congreso; ICPP Porphyrins and Porphyrias 2017; 2017

It was suggested a role for some CYP1A1 and CYP1A2 isoformes in PCT development but the results from different populations are controversial. We analysed three polymorphisms, 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 studied 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 frequencies of A alelle and A/A genotype were higher for both types of PCT vs control group, being the A allele associated to a more transcriptional activity of CYP1A2 gene. There were 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0.018) for total PCT vs control group. For CYP1A1*4A or m4 (c.4487 CA; p.T461N), C alelle and C/C genotype were the most frequent for total PCT vs control group. A significant difference 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 was observed for the hererozygous genotype vs A/A. 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 enzyme activity than wild type allele. Significant differences were found only for A-PCT vs control for A/A vs A/G genotypes (p0.0016). So, we conclude that these polymorphisms could be, among others, a risk factor for triggering PCT clinical signs in Argentinean population.