Polymorphisms of genes required for methionine synthesis and DNA methylation influence mitochondrial DNA methylation

Andrea Stoccoro; Pierpaola Tannorella; Lucia Migliore; Fabio Coppedè

doi:10.2217/epi-2020-0041

Polymorphisms of genes required for methionine synthesis and DNA methylation influence mitochondrial DNA methylation

Andrea Stoccoro, Pierpaola Tannorella, Lucia Migliore, Fabio Coppedè

Research output: Contribution to journal › Article › peer-review

Abstract

Aim: Impaired methylation of the mitochondrial DNA and particularly in the regulatory displacement loop (D-loop) region, is increasingly observed in patients with neurodegenerative disorders. The present study aims to investigate if common polymorphisms of genes required for one-carbon metabolism (MTHFR, MTRR, MTR and RFC-1) and DNA methylation reactions (DNMT1, DNMT3A and DNMT3B) influence D-loop methylation levels. Materials & methods: D-loop methylation data were available from 133 late-onset Alzheimer's disease patients and 130 matched controls. Genotyping was performed with PCR-RFLP or high resolution melting techniques. Results: Both MTRR 66A > G and DNMT3A -448A > G polymorphisms were significantly associated with D-loop methylation levels. Conclusion: This exploratory study suggests that MTRR and DNMT3A polymorphisms influence mitochondrial DNA methylation; further research is required to better address this issue.

Original language	English
Pages (from-to)	1003-1012
Number of pages	10
Journal	Epigenomics
Volume	12
Issue number	12
DOIs	https://doi.org/10.2217/epi-2020-0041
Publication status	Published - Jun 2020

Keywords

Alzheimer's disease
D-loop methylation
DNMT3A
mitochondrial DNA methylation
mitoepigenetics
MTHFR
MTR
MTRR
polymorphism
RFC-1

ASJC Scopus subject areas

Genetics
Cancer Research

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@article{2e5cb66984014bbda69753699660e00b,

title = "Polymorphisms of genes required for methionine synthesis and DNA methylation influence mitochondrial DNA methylation",

abstract = "Aim: Impaired methylation of the mitochondrial DNA and particularly in the regulatory displacement loop (D-loop) region, is increasingly observed in patients with neurodegenerative disorders. The present study aims to investigate if common polymorphisms of genes required for one-carbon metabolism (MTHFR, MTRR, MTR and RFC-1) and DNA methylation reactions (DNMT1, DNMT3A and DNMT3B) influence D-loop methylation levels. Materials & methods: D-loop methylation data were available from 133 late-onset Alzheimer's disease patients and 130 matched controls. Genotyping was performed with PCR-RFLP or high resolution melting techniques. Results: Both MTRR 66A > G and DNMT3A -448A > G polymorphisms were significantly associated with D-loop methylation levels. Conclusion: This exploratory study suggests that MTRR and DNMT3A polymorphisms influence mitochondrial DNA methylation; further research is required to better address this issue. ",

keywords = "Alzheimer's disease, D-loop methylation, DNMT3A, mitochondrial DNA methylation, mitoepigenetics, MTHFR, MTR, MTRR, polymorphism, RFC-1",

author = "Andrea Stoccoro and Pierpaola Tannorella and Lucia Migliore and Fabio Copped{\`e}",

note = "Funding Information: This work was partially supported by the Italian Ministry of Health (grant GR-2009-1606229 to F Copped{\`e}) and by the senior researcher{\textquoteright}s intramural funds (ATENEO Funds 2018, University of Pisa). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. Publisher Copyright: {\textcopyright} 2020 Future Medicine Ltd. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2020",

month = jun,

doi = "10.2217/epi-2020-0041",

language = "English",

volume = "12",

pages = "1003--1012",

journal = "Epigenomics",

issn = "1750-1911",

publisher = "Future Medicine Ltd.",

number = "12",

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TY - JOUR

T1 - Polymorphisms of genes required for methionine synthesis and DNA methylation influence mitochondrial DNA methylation

AU - Stoccoro, Andrea

AU - Tannorella, Pierpaola

AU - Migliore, Lucia

AU - Coppedè, Fabio

N1 - Funding Information: This work was partially supported by the Italian Ministry of Health (grant GR-2009-1606229 to F Coppedè) and by the senior researcher’s intramural funds (ATENEO Funds 2018, University of Pisa). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. Publisher Copyright: © 2020 Future Medicine Ltd. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/6

Y1 - 2020/6

N2 - Aim: Impaired methylation of the mitochondrial DNA and particularly in the regulatory displacement loop (D-loop) region, is increasingly observed in patients with neurodegenerative disorders. The present study aims to investigate if common polymorphisms of genes required for one-carbon metabolism (MTHFR, MTRR, MTR and RFC-1) and DNA methylation reactions (DNMT1, DNMT3A and DNMT3B) influence D-loop methylation levels. Materials & methods: D-loop methylation data were available from 133 late-onset Alzheimer's disease patients and 130 matched controls. Genotyping was performed with PCR-RFLP or high resolution melting techniques. Results: Both MTRR 66A > G and DNMT3A -448A > G polymorphisms were significantly associated with D-loop methylation levels. Conclusion: This exploratory study suggests that MTRR and DNMT3A polymorphisms influence mitochondrial DNA methylation; further research is required to better address this issue.

AB - Aim: Impaired methylation of the mitochondrial DNA and particularly in the regulatory displacement loop (D-loop) region, is increasingly observed in patients with neurodegenerative disorders. The present study aims to investigate if common polymorphisms of genes required for one-carbon metabolism (MTHFR, MTRR, MTR and RFC-1) and DNA methylation reactions (DNMT1, DNMT3A and DNMT3B) influence D-loop methylation levels. Materials & methods: D-loop methylation data were available from 133 late-onset Alzheimer's disease patients and 130 matched controls. Genotyping was performed with PCR-RFLP or high resolution melting techniques. Results: Both MTRR 66A > G and DNMT3A -448A > G polymorphisms were significantly associated with D-loop methylation levels. Conclusion: This exploratory study suggests that MTRR and DNMT3A polymorphisms influence mitochondrial DNA methylation; further research is required to better address this issue.

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KW - polymorphism

KW - RFC-1

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