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

LUBNA. ABOU ASSALI; DIEGO M. GORDILLO ; GABRIELA N. CERBINO ; LAURA S. VARELA; VICTORIA E. PARERA ; MARÍA V. ROSSETTI

European Journal of Molecular & Clinical Medicine

UBIQUITY PRESS

Año: 2020

Acute intermittent porphyria (AIP) is a metabolic disease caused by a deficiency of hydroxymethylbilane synthase (HMBS), one of the eight enzymes involved in the haem biosynthesis pathway. 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, endocrine factors, fasting or stress. Genetic susceptibility factors underlying penetrance are still unknown. Drug-metabolizing cytochrome P450 isoform, CYP2C9 is a polymorphic haem-dependent enzyme which plays a role in haem demand and might modulate the occurrence of AIP attacks. The aim of this study was to assess the levels of biochemical markers in 63 Argentinean AIP patients who carried different variants of CYP2C9. It was observed that, in AIP men the triggering factor was medicinal drugs consumption. In contrast, 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 with CYP2C9*1/*1 carriers. Worldwide, this study has demonstrated, for the first time, that AIP men carriers CYPC9*1/*2 could have a high possibility to trigger the disease due to porphyrinogenic drugs consumption, highlighting the importance of personalized medical advice in the field of porphyria, to advise them about the danger of the consumption of porphyrinogenic agents that could lead to a fatal outcome.