Cargando…

Methylated Cytochrome P450 and the Solute Carrier Family of Genes Correlate With Perturbations in Bile Acid Metabolism in Parkinson’s Disease

Parkinson’s disease (PD) is second most prevalent neurodegenerative disorder following Alzheimer’s disease. Parkinson’s disease is hypothesized to be caused by a multifaceted interplay between genetic and environmental factors. Herein, and for the first time, we describe the integration of metabolom...

Descripción completa

Detalles Bibliográficos
Autores principales: Vishweswaraiah, Sangeetha, Akyol, Sumeyya, Yilmaz, Ali, Ugur, Zafer, Gordevičius, Juozas, Oh, Kyung Joon, Brundin, Patrik, Radhakrishna, Uppala, Labrie, Viviane, Graham, Stewart F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9009246/
https://www.ncbi.nlm.nih.gov/pubmed/35431771
http://dx.doi.org/10.3389/fnins.2022.804261
_version_ 1784687229537353728
author Vishweswaraiah, Sangeetha
Akyol, Sumeyya
Yilmaz, Ali
Ugur, Zafer
Gordevičius, Juozas
Oh, Kyung Joon
Brundin, Patrik
Radhakrishna, Uppala
Labrie, Viviane
Graham, Stewart F.
author_facet Vishweswaraiah, Sangeetha
Akyol, Sumeyya
Yilmaz, Ali
Ugur, Zafer
Gordevičius, Juozas
Oh, Kyung Joon
Brundin, Patrik
Radhakrishna, Uppala
Labrie, Viviane
Graham, Stewart F.
author_sort Vishweswaraiah, Sangeetha
collection PubMed
description Parkinson’s disease (PD) is second most prevalent neurodegenerative disorder following Alzheimer’s disease. Parkinson’s disease is hypothesized to be caused by a multifaceted interplay between genetic and environmental factors. Herein, and for the first time, we describe the integration of metabolomics and epigenetics (genome-wide DNA methylation; epimetabolomics) to profile the frontal lobe from people who died from PD and compared them with age-, and sex-matched controls. We identified 48 metabolites to be at significantly different concentrations (FDR q < 0.05), 4,313 differentially methylated sites [5’-C-phosphate-G-3’ (CpGs)] (FDR q < 0.05) and increased DNA methylation age in the primary motor cortex of people who died from PD. We identified Primary bile acid biosynthesis as the major biochemical pathway to be perturbed in the frontal lobe of PD sufferers, and the metabolite taurine (p-value = 5.91E-06) as being positively correlated with CpG cg14286187 (SLC25A27; CYP39A1) (FDR q = 0.002), highlighting previously unreported biochemical changes associated with PD pathogenesis. In this novel multi-omics study, we identify regulatory mechanisms which we believe warrant future translational investigation and central biomarkers of PD which require further validation in more accessible biomatrices.
format Online
Article
Text
id pubmed-9009246
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-90092462022-04-15 Methylated Cytochrome P450 and the Solute Carrier Family of Genes Correlate With Perturbations in Bile Acid Metabolism in Parkinson’s Disease Vishweswaraiah, Sangeetha Akyol, Sumeyya Yilmaz, Ali Ugur, Zafer Gordevičius, Juozas Oh, Kyung Joon Brundin, Patrik Radhakrishna, Uppala Labrie, Viviane Graham, Stewart F. Front Neurosci Neuroscience Parkinson’s disease (PD) is second most prevalent neurodegenerative disorder following Alzheimer’s disease. Parkinson’s disease is hypothesized to be caused by a multifaceted interplay between genetic and environmental factors. Herein, and for the first time, we describe the integration of metabolomics and epigenetics (genome-wide DNA methylation; epimetabolomics) to profile the frontal lobe from people who died from PD and compared them with age-, and sex-matched controls. We identified 48 metabolites to be at significantly different concentrations (FDR q < 0.05), 4,313 differentially methylated sites [5’-C-phosphate-G-3’ (CpGs)] (FDR q < 0.05) and increased DNA methylation age in the primary motor cortex of people who died from PD. We identified Primary bile acid biosynthesis as the major biochemical pathway to be perturbed in the frontal lobe of PD sufferers, and the metabolite taurine (p-value = 5.91E-06) as being positively correlated with CpG cg14286187 (SLC25A27; CYP39A1) (FDR q = 0.002), highlighting previously unreported biochemical changes associated with PD pathogenesis. In this novel multi-omics study, we identify regulatory mechanisms which we believe warrant future translational investigation and central biomarkers of PD which require further validation in more accessible biomatrices. Frontiers Media S.A. 2022-03-31 /pmc/articles/PMC9009246/ /pubmed/35431771 http://dx.doi.org/10.3389/fnins.2022.804261 Text en Copyright © 2022 Vishweswaraiah, Akyol, Yilmaz, Ugur, Gordevičius, Oh, Brundin, Radhakrishna, Labrie and Graham. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Vishweswaraiah, Sangeetha
Akyol, Sumeyya
Yilmaz, Ali
Ugur, Zafer
Gordevičius, Juozas
Oh, Kyung Joon
Brundin, Patrik
Radhakrishna, Uppala
Labrie, Viviane
Graham, Stewart F.
Methylated Cytochrome P450 and the Solute Carrier Family of Genes Correlate With Perturbations in Bile Acid Metabolism in Parkinson’s Disease
title Methylated Cytochrome P450 and the Solute Carrier Family of Genes Correlate With Perturbations in Bile Acid Metabolism in Parkinson’s Disease
title_full Methylated Cytochrome P450 and the Solute Carrier Family of Genes Correlate With Perturbations in Bile Acid Metabolism in Parkinson’s Disease
title_fullStr Methylated Cytochrome P450 and the Solute Carrier Family of Genes Correlate With Perturbations in Bile Acid Metabolism in Parkinson’s Disease
title_full_unstemmed Methylated Cytochrome P450 and the Solute Carrier Family of Genes Correlate With Perturbations in Bile Acid Metabolism in Parkinson’s Disease
title_short Methylated Cytochrome P450 and the Solute Carrier Family of Genes Correlate With Perturbations in Bile Acid Metabolism in Parkinson’s Disease
title_sort methylated cytochrome p450 and the solute carrier family of genes correlate with perturbations in bile acid metabolism in parkinson’s disease
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9009246/
https://www.ncbi.nlm.nih.gov/pubmed/35431771
http://dx.doi.org/10.3389/fnins.2022.804261
work_keys_str_mv AT vishweswaraiahsangeetha methylatedcytochromep450andthesolutecarrierfamilyofgenescorrelatewithperturbationsinbileacidmetabolisminparkinsonsdisease
AT akyolsumeyya methylatedcytochromep450andthesolutecarrierfamilyofgenescorrelatewithperturbationsinbileacidmetabolisminparkinsonsdisease
AT yilmazali methylatedcytochromep450andthesolutecarrierfamilyofgenescorrelatewithperturbationsinbileacidmetabolisminparkinsonsdisease
AT ugurzafer methylatedcytochromep450andthesolutecarrierfamilyofgenescorrelatewithperturbationsinbileacidmetabolisminparkinsonsdisease
AT gordeviciusjuozas methylatedcytochromep450andthesolutecarrierfamilyofgenescorrelatewithperturbationsinbileacidmetabolisminparkinsonsdisease
AT ohkyungjoon methylatedcytochromep450andthesolutecarrierfamilyofgenescorrelatewithperturbationsinbileacidmetabolisminparkinsonsdisease
AT brundinpatrik methylatedcytochromep450andthesolutecarrierfamilyofgenescorrelatewithperturbationsinbileacidmetabolisminparkinsonsdisease
AT radhakrishnauppala methylatedcytochromep450andthesolutecarrierfamilyofgenescorrelatewithperturbationsinbileacidmetabolisminparkinsonsdisease
AT labrieviviane methylatedcytochromep450andthesolutecarrierfamilyofgenescorrelatewithperturbationsinbileacidmetabolisminparkinsonsdisease
AT grahamstewartf methylatedcytochromep450andthesolutecarrierfamilyofgenescorrelatewithperturbationsinbileacidmetabolisminparkinsonsdisease