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The association of DAT gene methylation with striatal DAT availability in healthy subjects

BACKGROUND: DNA methylation inhibits gene expression by preventing transcription factors from binding to DNA. Functioning of nigrostriatal dopaminergic neurons is influenced by the expression of the dopamine transporter (DAT), and genetic variations in the gene encoding DAT contribute to differences...

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Autores principales: Pak, Kyoungjune, Seok, Ju Won, Nam, Hyun-Yeol, Seo, Seongho, Lee, Myung Jun, Kim, Keunyoung, Kim, In Joo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197693/
https://www.ncbi.nlm.nih.gov/pubmed/34120227
http://dx.doi.org/10.1186/s13550-021-00800-y
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author Pak, Kyoungjune
Seok, Ju Won
Nam, Hyun-Yeol
Seo, Seongho
Lee, Myung Jun
Kim, Keunyoung
Kim, In Joo
author_facet Pak, Kyoungjune
Seok, Ju Won
Nam, Hyun-Yeol
Seo, Seongho
Lee, Myung Jun
Kim, Keunyoung
Kim, In Joo
author_sort Pak, Kyoungjune
collection PubMed
description BACKGROUND: DNA methylation inhibits gene expression by preventing transcription factors from binding to DNA. Functioning of nigrostriatal dopaminergic neurons is influenced by the expression of the dopamine transporter (DAT), and genetic variations in the gene encoding DAT contribute to differences in reward processing. We aimed to investigate the action of DAT methylation on DAT protein expression measured by positron emission tomography (PET). METHODS: The emission data were acquired over 90 min with 50 frames after injection of (18)F-FP-CIT using PET. Binding potentials (BP(ND)s) of ventral striatum, caudate nucleus, putamen were measured with the simplified reference tissue method. Genomic DNA was extracted from subjects’ blood sampling. Methylation of 4 regions in SLC6A3 gene was assessed using bisulfite pyrosequencing. The mean percentage of methylation (%) for each cluster was calculated by taking the average of all CpG site methylation levels measured within the cluster. Subjects were assessed with the Generalized Reward and Punishment Expectancy Scales (GRAPES) that consists of 30 items related with the reward and punishment that individuals expect for their behaviors. RESULTS: Thirty-five healthy males, with an age range between 20 and 30 years, and a mean age of 24.4 ± 2.7 years, were included in this study. The mean percentage of methylation (%) from cluster C showed a trend of positive correlation with DAT availability of ventral striatum (rho = 0.3712, p = 0.0281), not significant after correction for multiple comparisons, and a significant correlation with GRAPES A: reward expectancy scale (rho = 0.7178, p < 0.0001). CONCLUSION: DAT methylation from peripheral blood showed a trend of positive correlation with DAT availability of ventral striatum in healthy subjects; however, it was not significant after correction for multiple comparison. The degrees of methylation from cluster C of DAT in peripheral blood were significantly correlated with reward scales of GRAPES A: reward expectancy scale. The association between DAT methylation and DAT expression needs to be investigated further.
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spelling pubmed-81976932021-06-28 The association of DAT gene methylation with striatal DAT availability in healthy subjects Pak, Kyoungjune Seok, Ju Won Nam, Hyun-Yeol Seo, Seongho Lee, Myung Jun Kim, Keunyoung Kim, In Joo EJNMMI Res Original Research BACKGROUND: DNA methylation inhibits gene expression by preventing transcription factors from binding to DNA. Functioning of nigrostriatal dopaminergic neurons is influenced by the expression of the dopamine transporter (DAT), and genetic variations in the gene encoding DAT contribute to differences in reward processing. We aimed to investigate the action of DAT methylation on DAT protein expression measured by positron emission tomography (PET). METHODS: The emission data were acquired over 90 min with 50 frames after injection of (18)F-FP-CIT using PET. Binding potentials (BP(ND)s) of ventral striatum, caudate nucleus, putamen were measured with the simplified reference tissue method. Genomic DNA was extracted from subjects’ blood sampling. Methylation of 4 regions in SLC6A3 gene was assessed using bisulfite pyrosequencing. The mean percentage of methylation (%) for each cluster was calculated by taking the average of all CpG site methylation levels measured within the cluster. Subjects were assessed with the Generalized Reward and Punishment Expectancy Scales (GRAPES) that consists of 30 items related with the reward and punishment that individuals expect for their behaviors. RESULTS: Thirty-five healthy males, with an age range between 20 and 30 years, and a mean age of 24.4 ± 2.7 years, were included in this study. The mean percentage of methylation (%) from cluster C showed a trend of positive correlation with DAT availability of ventral striatum (rho = 0.3712, p = 0.0281), not significant after correction for multiple comparisons, and a significant correlation with GRAPES A: reward expectancy scale (rho = 0.7178, p < 0.0001). CONCLUSION: DAT methylation from peripheral blood showed a trend of positive correlation with DAT availability of ventral striatum in healthy subjects; however, it was not significant after correction for multiple comparison. The degrees of methylation from cluster C of DAT in peripheral blood were significantly correlated with reward scales of GRAPES A: reward expectancy scale. The association between DAT methylation and DAT expression needs to be investigated further. Springer Berlin Heidelberg 2021-06-12 /pmc/articles/PMC8197693/ /pubmed/34120227 http://dx.doi.org/10.1186/s13550-021-00800-y Text en © The Author(s) 2021, Article corrected in 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Research
Pak, Kyoungjune
Seok, Ju Won
Nam, Hyun-Yeol
Seo, Seongho
Lee, Myung Jun
Kim, Keunyoung
Kim, In Joo
The association of DAT gene methylation with striatal DAT availability in healthy subjects
title The association of DAT gene methylation with striatal DAT availability in healthy subjects
title_full The association of DAT gene methylation with striatal DAT availability in healthy subjects
title_fullStr The association of DAT gene methylation with striatal DAT availability in healthy subjects
title_full_unstemmed The association of DAT gene methylation with striatal DAT availability in healthy subjects
title_short The association of DAT gene methylation with striatal DAT availability in healthy subjects
title_sort association of dat gene methylation with striatal dat availability in healthy subjects
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197693/
https://www.ncbi.nlm.nih.gov/pubmed/34120227
http://dx.doi.org/10.1186/s13550-021-00800-y
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