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

Abstract

Porphyria Cutanea Tarda (PCT) is due to a partial deficiency in uroporphyrinogen decarboxylase (URO-D); there are two main types: hereditary (H-PCT) or acquired (A-PCT). The cytochrome variants P-450, CYP1A1 and CYP1A2 alter their drug metabolizing capacity generating metabolites that can inhibit URO-D, increasing susceptibility to trigger Porphyria. The product of the CYP2E1 variant metabolizes ethanol, known as a porphyrinogenic agent. The objective was to 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 sequenced when the band pattern was unclear. When we analized CYP2E1*5B, the frequencies of the reference homozygote were similar to those of the heterozygote, the alternative homozygote were not present and C allele was the most common. There was no significant risk association between this variant and PCT. Studying CYP2E1*7B, the reference homozygotes genotypes were more frequent than heterozygotes and both have higher frequencies than alternative homozygotes; the frequency of G/T was significantly higher in H-PCT individuals compared to A-PCT (p=0.045), being the reference allele the most frequent. Comparing H-PCT vs A-PCT, G/T vs G/G gave a significant risk association (OR=4.11; 1.01<CI<17.2; p=0.044), being T allele for these same groups of not significant risk. The study of risk haplotypes for CYP2E1*5B/*7B in both types of PCT vs control gave T-T (non-significant differences). Since both variants are associated with an increase in transcriptional activity of CYP2E1 gene, it is suggested that they could be a risk factor to trigger PCT. These studies are valuable for personalized medical advice in order to prevent carriers from being exposed to porphyrinogenic agents.