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DNA methylation of the 5′‐UTR DAT 1 gene in Parkinson's disease patients.

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Title: DNA methylation of the 5′‐UTR DAT 1 gene in Parkinson's disease patients.
Authors: Rubino, Alfonso (AUTHOR), D'Addario, Claudio (AUTHOR), Di Bartolomeo, Martina (AUTHOR), Michele Salamone, Enrico (AUTHOR), Locuratolo, Nicoletta (AUTHOR), Fattapposta, Francesco (AUTHOR), Vanacore, Nicola (AUTHOR), Pascale, Esterina (AUTHOR)
Source: Acta Neurologica Scandinavica. Sep2020, Vol. 142 Issue 3, p275-280. 6p.
Subjects: DNA methylation, Parkinson's disease, Dopaminergic neurons, Regression analysis, p16 gene, Statistical significance
Abstract: Objectives: The involvement of epigenetics mechanisms in the transcriptional regulation of key genes has been investigated in the initiation and progression of neurodegenerative disorders, including Parkinson's disease (PD). Among others, we, here, focused the attention on the dopamine transporter (DAT) gene playing a critical role in maintaining the integrity of dopaminergic neurons. Materials and Methods: We performed bisulfite pyrosequencing to examine DNA methylation levels of six CpG sites in the 5′‐UTR of DAT1 gene in human peripheral blood mononuclear cells (PBMCs) obtained from 101 sporadic PD patients and 59 healthy controls. Results: We selectively report for CpG5 an increase in DNA methylation levels in PD subjects respect to controls, that almost reaches statistical significance (30.06 ± 12.4 vs 26.58 ± 7.6, P =.052). Of interest, a significantly higher methylation at specific CpG sites (ANOVA: P =.029) was observed in PD subjects with advanced stage of illness. Namely, a multivariate regression analysis showed that a higher methylation level at specific CpG sites in the group of PD patients was associated with increased methylation at CpG2, CpG3, and with H&Y stage but not with age and gender. This regression model explains the 38% of the variance of methylation at CpG5. Conclusion: Our results do seem to suggest that the methylation level of CpG5 is different between PD patients and controls. Moreover, this methylation level for CpG5 may be associated also with the stage of disease. [ABSTRACT FROM AUTHOR]
Copyright of Acta Neurologica Scandinavica is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: DNA methylation of the 5′‐UTR DAT 1 gene in Parkinson's disease patients.
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  Data: <searchLink fieldCode="AR" term="%22Rubino%2C+Alfonso%22">Rubino, Alfonso</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22D'Addario%2C+Claudio%22">D'Addario, Claudio</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Di+Bartolomeo%2C+Martina%22">Di Bartolomeo, Martina</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Michele+Salamone%2C+Enrico%22">Michele Salamone, Enrico</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Locuratolo%2C+Nicoletta%22">Locuratolo, Nicoletta</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Fattapposta%2C+Francesco%22">Fattapposta, Francesco</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Vanacore%2C+Nicola%22">Vanacore, Nicola</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Pascale%2C+Esterina%22">Pascale, Esterina</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22Acta+Neurologica+Scandinavica%22">Acta Neurologica Scandinavica</searchLink>. Sep2020, Vol. 142 Issue 3, p275-280. 6p.
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  Data: <searchLink fieldCode="DE" term="%22DNA+methylation%22">DNA methylation</searchLink><br /><searchLink fieldCode="DE" term="%22Parkinson's+disease%22">Parkinson's disease</searchLink><br /><searchLink fieldCode="DE" term="%22Dopaminergic+neurons%22">Dopaminergic neurons</searchLink><br /><searchLink fieldCode="DE" term="%22Regression+analysis%22">Regression analysis</searchLink><br /><searchLink fieldCode="DE" term="%22p16+gene%22">p16 gene</searchLink><br /><searchLink fieldCode="DE" term="%22Statistical+significance%22">Statistical significance</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Objectives: The involvement of epigenetics mechanisms in the transcriptional regulation of key genes has been investigated in the initiation and progression of neurodegenerative disorders, including Parkinson's disease (PD). Among others, we, here, focused the attention on the dopamine transporter (DAT) gene playing a critical role in maintaining the integrity of dopaminergic neurons. Materials and Methods: We performed bisulfite pyrosequencing to examine DNA methylation levels of six CpG sites in the 5′‐UTR of DAT1 gene in human peripheral blood mononuclear cells (PBMCs) obtained from 101 sporadic PD patients and 59 healthy controls. Results: We selectively report for CpG5 an increase in DNA methylation levels in PD subjects respect to controls, that almost reaches statistical significance (30.06 ± 12.4 vs 26.58 ± 7.6, P =.052). Of interest, a significantly higher methylation at specific CpG sites (ANOVA: P =.029) was observed in PD subjects with advanced stage of illness. Namely, a multivariate regression analysis showed that a higher methylation level at specific CpG sites in the group of PD patients was associated with increased methylation at CpG2, CpG3, and with H&Y stage but not with age and gender. This regression model explains the 38% of the variance of methylation at CpG5. Conclusion: Our results do seem to suggest that the methylation level of CpG5 is different between PD patients and controls. Moreover, this methylation level for CpG5 may be associated also with the stage of disease. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
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  Data: <i>Copyright of Acta Neurologica Scandinavica is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1111/ane.13279
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        Text: English
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      – SubjectFull: Dopaminergic neurons
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      – SubjectFull: Regression analysis
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      – SubjectFull: Statistical significance
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      – TitleFull: DNA methylation of the 5′‐UTR DAT 1 gene in Parkinson's disease patients.
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              Text: Sep2020
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