Heme Biosynthetic Gene Expression Analysis With dPCR in Erythropoietic Protoporphyria Patients.

Autor:	Granata F; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, U.O.C. Medicina Generale, Milano, Italy., Brancaleoni V; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, U.O.C. Medicina Generale, Milano, Italy., Barman-Aksözen J; Department of Medical Institutes, Institute of Laboratory Medicine, Stadtspital Zürich, Zürich, Switzerland., Scopetti M; Università degli Studi di Milano, Milan, Italy., De Luca G; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, U.O.C. Medicina Generale, Milano, Italy., Fustinoni S; EPIGET-Epidemiology, Epigenetics, and Toxicology Lab, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, U.O.S Tossicologia, Università degli Studi di Milano, Milan, Italy., Motta I; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, U.O.C. Medicina Generale, Milano, Italy.; Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy., Di Pierro E; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, U.O.C. Medicina Generale, Milano, Italy., Graziadei G; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, U.O.C. Medicina Generale, Milano, Italy.
Jazyk:	angličtina
Zdroj:	Frontiers in physiology [Front Physiol] 2022 Jul 18; Vol. 13, pp. 886194. Date of Electronic Publication: 2022 Jul 18 (Print Publication: 2022).
DOI:	10.3389/fphys.2022.886194
Abstrakt:	Background: The heme biosynthesis (HB) involves eight subsequent enzymatic steps. Erythropoietic protoporphyria (EPP) is caused by loss-of-function mutations in the ferrochelatase (FECH) gene, which in the last HB step inserts ferrous iron into protoporphyrin IX (PPIX) to form heme. Aim and method: The aim of this work was to for the first time analyze the mRNA expression of all HB genes in peripheral blood samples of patients with EPP having the same genotype FECH c.[215dupT]; [315-48T > C] as compared to healthy controls by highly sensitive and specific digital PCR assays (dPCR). Results: We confirmed a decreased FECH mRNA expression in patients with EPP. Further, we found increased ALAS2 and decreased ALAS1, CPOX, PPOX and HMBS mRNA expression in patients with EPP compared to healthy controls. ALAS2 correlated with FECH mRNA expression (EPP: r = 0.63, p = 0.03 and controls: r = 0.68, p = 0.02) and blood parameters like PPIX (EPP: r = 0.58 p = 0.06). Conclusion: Our method is the first that accurately quantifies HB mRNA from blood samples with potential applications in the monitoring of treatment effects of mRNA modifying therapies in vivo , or investigation of the HB pathway and its regulation. However, our findings should be studied in separated blood cell fractions and on the enzymatic level. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Granata, Brancaleoni, Barman-Aksözen, Scopetti, De Luca, Fustinoni, Motta, Di Pierro and Graziadei.)
Databáze:	MEDLINE
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