High Level of Haem Precursors in AIP Men Carrying CYP2C9*1/*2 Haplotype

CERBINO G N; ROSSETTI MV; GORDILLO D M; PARERA VE; ABOU ASSALI L; VARELA L S

European Journal of Molecular & Clinical Medicine

European Society for Translational Medicine

Lugar: Londres; Año: 2020 p. 1 - 7

2515-8260

Abstract: Acute intermittent porphyria (AIP) is a metabolic disease caused by a deficiency ofhydroxymethylbilane synthase (HMBS), one of the eight enzymes involved in the haem biosynthesispathway. In Argentina, the most predominant pathogenic variant is NG_008093.1:g.9871G>A(rs118204107). There are many factors that lead to the manifestation of AIP such as: drugs, endocrinefactors, fasting or stress. Genetic susceptibility factors underlying penetrance are still unknown. Drug-metabolizing cytochrome P450 isoform; CYP2C9 is a polymorphic haem-dependent enzyme which playsa role in haem demand and might modulate the occurrence of AIP attacks. The aim of this study was toassess the levels of biochemical markers in 63 Argentinean AIP patients who carried different variantsof CYP2C9. It was observed that, in AIP men; the triggering factor was drugs consumption. Incontrast, in AIP women the manifestation was due to various reasons, mainly contraceptives intake(OCs). AIP men carrying CYP2C9*1/*2 had higher levels of haem precursors compared withCYP2C9*1/*1 carriers. Worldwide, this study has demonstrated, for the first time, that AIP mencarriers CYPC9*1/*2 could have a high possibility to trigger the disease due to porphyrinogenic drugsconsumption, highlighting the importance of personalized medical advice in the field of porphyria, toadvise them about the danger of the consumption of porphyrinogenic agents that could lead to a fataloutcome.