Science and Technology Production
High level of haem precursors in AIP men carrying CYP2C9 1/ 2 haplotype
Article
Authorship:
Abou Assaly Lubna ; Gordillo Diego Miguel ; Cerbino Gabriela ; Varela Laura ; PARERA, VICTORIA ESTELA ; Rossetti María VictoriaDate:
2020Publishing House and Editing Place:
formerly handled by ElsevierMagazine:
European Journal of molecular and clinical medicine - ISSN 2515-8260formerly handled by Elsevier
ISSN:
2515-8260Summary *
Acute intermittent porphyria (AIP) is a metabolic disease caused by a deficiency of hydroxymethylbilanesynthase (HMBS), one of the eight enzymes involved in the haem biosynthesis pathway. In Argentina, themost predominant pathogenic variant is NG_008093.1:g.9871G>A (rs118204107). There are manyfactors that lead to the manifestation of AIP such as: drugs, endocrine factors, fasting or stress. Geneticsusceptibility factors underlying penetrance are still unknown. Drug-metabolizing cytochrome P450isoform; CYP2C9 is a polymorphic haem-dependent enzyme which plays a role in haem demand andmight modulate the occurrence of AIP attacks. The aim of this study was to assess the levels ofbiochemical markers in 63 Argentinean AIP patients who carried different variants of CYP2C9. It wasobserved that, in AIP men; the triggering factor was drugs consumption. In contrast, in AIP women themanifestation was due to various reasons, mainly contraceptives intake (OCs). AIP men carryingCYP2C9*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 highpossibility to trigger the disease due to porphyrinogenic drugs consumption, highlighting the importanceof personalized medical advice in the field of porphyria, to advise them about the danger of theconsumption of porphyrinogenic agents that could lead to a fatal outcome. Information provided by the agent in SIGEVAKey Words
ACUTE INTERMITENT PORPHYRIA (AIP)CYP2C9CYP450AIP TRIGGERING