Genetic variants of CYP2E1 and its relationship with Porphyria Cutanea Tarda development

DIEGO MIGUEL GORDILLO; LUBNA ABOU ASSALI; LAURA SABINA VARELA; GABRIELA NORA CERBINO; VICTORIA ESTELA PARERA; MARÍA VICTORIA ROSSETTI; ANA MARÍA BUZALEH

Otro; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2020; 2020

SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA

Porphyria Cutanea Tarda (PCT) is due to a partial deficiency in uroporphyrinogendecarboxylase (URO-D); there are two main types:hereditary (H-PCT) or acquired (A-PCT). The cytochrome variantsP-450, CYP1A1 and CYP1A2 alter their drug metabolizing capacitygenerating metabolites that can inhibit URO-D, increasing susceptibilityto trigger Porphyria. The product of the CYP2E1 variant metabolizesethanol, known as a porphyrinogenic agent. The objective wasto investigate the role of CYP2E1*5B (NG_008383.1:g.3979C>T;rs2031920) and CYP2E1*7B (NG_008383.1:g.4963G>T;rs6413420) variants in PCT development. H-PCT (30), A-PCT (31)and control (33) groups were genotyped by RFLP-PCR and sequencedwhen the band pattern was unclear. When we analizedCYP2E1*5B, the frequencies of the reference homozygote weresimilar to those of the heterozygote, the alternative homozygotewere not present and C allele was the most common. There was nosignificant risk association between this variant and PCT. StudyingCYP2E1*7B, the reference homozygotes genotypes were more frequentthan heterozygotes and both have higher frequencies than alternativehomozygotes; the frequency of G/T was significantly higherin H-PCT individuals compared to A-PCT (p=0.045), being thereference allele the most frequent. Comparing H-PCT vs A-PCT, G/Tvs G/G gave a significant risk association (OR=4.11; 1.01