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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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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 |
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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 |
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