Open AccessTranscriptomic study in explanted liver from a patient with acute intermittent porphyria
Author(s) -
ToFigueras Jordi,
Titos Esther,
Aguilera Paula,
Díaz Alba,
MuñozLuque Javier,
Madrigal Irene,
Badenas Celia,
Torra Mercè,
Fondevila Constantino,
Colmenero Jordi
Publication year - 2023
Publication title -
jimd reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.412
H-Index - 25
ISSN - 2192-8312
DOI - 10.1002/jmd2.12329
Subject(s) - hmox1 , transcriptome , porphobilinogen deaminase , porphyria , acute intermittent porphyria , biology , heme , microbiology and biotechnology , porphobilinogen synthase , gene , gene expression , heme oxygenase , enzyme , endocrinology , biochemistry , dehydratase
Acute intermittent porphyria (AIP) is a rare disease caused by a deficiency of hydroxymethylbilane synthase (HMBS), the third enzyme of the heme‐synthesis pathway. Decreased enzymatic activity in the liver induces an overproduction of heme‐precursors and acute neurological attacks. We report a 36‐years‐old female with AIP with a long‐term history of severe, disabling, recurrent attacks, who underwent curative liver transplantation. Tissue samples from the explant were obtained for transcriptome analysis. Whole RNA was extracted and 16 gene‐transcripts were selected and investigated by quantitative polymerase chain reaction. These included nine genes encoding enzymes that consecutively catalyze heme‐synthesis and catabolism in the liver ( ALAS1 ; ALAD ; HMBS ; UROS ; UROD ; CPOX ; PPOX ; FECH ; HMOX1 ). Additionally, we studied genes related to inflammation ( IL6 ; TNF ) insulin signaling ( PGC‐1α ; IGF‐1 ; FOXO‐1 ) and tryptophan metabolism ( TDO2 ; IDO ). Transcripts of eight house‐keeping genes were co‐measured for normalization. All transcripts were also measured in five control samples from healthy living liver donors. The transcriptome of the controls showed important differences between the various genes, with the first two genes of the heme‐synthesis pathway, ALAS1 and ALAD showing strikingly high mRNA levels compared to the consecutive HMBS gene. Transcripts of several genes significantly differed in the AIP liver compared to controls. Transcripts of HMOX1 and UROS were increased in the AIP liver whereas transcripts of UROD ; CPOX , PPOX , and TDO2 were decreased. ALAS1 expression was not increased, possibly due to hemin administered to the patient before transplantation. These results highlight several transcriptomic changes related to heme homeostasis in AIP.