Association of mitochondrial DNA copy number with metabolic syndrome and type 2 diabetes in 14 176 individuals.

Aged Body Mass Index Cross-Sectional Studies DNA Copy Number Variations DNA, Mitochondrial / genetics Diabetes Mellitus, Type 2 / complications Female Humans Male Metabolic Syndrome / complications Middle Aged Prospective Studies Triglycerides / blood Waist Circumference
chronic kidney disease diabetes metabolic syndrome mitochondrial DNA copy number

Journal

Journal of internal medicine
ISSN: 1365-2796
Titre abrégé: J Intern Med
Pays: England
ID NLM: 8904841

Informations de publication

Date de publication:
07 2021
Historique:
revised: 24 11 2020
received: 18 10 2020
accepted: 14 12 2020
pubmed: 17 1 2021
medline: 7 10 2021
entrez: 16 1 2021
Statut: ppublish

Résumé

Mitochondria play an important role in cellular metabolism, and their dysfunction is postulated to be involved in metabolic disturbances. Mitochondrial DNA is present in multiple copies per cell. The quantification of mitochondrial DNA copy number (mtDNA-CN) might be used to assess mitochondrial dysfunction. We aimed to investigate the cross-sectional association of mtDNA-CN with type 2 diabetes and the potential mediating role of metabolic syndrome. We examined 4812 patients from the German Chronic Kidney Disease (GCKD) study and 9364 individuals from the Cooperative Health Research in South Tyrol (CHRIS) study. MtDNA-CN was measured in whole blood using a plasmid-normalized qPCR-based assay. In both studies, mtDNA-CN showed a significant correlation with most metabolic syndrome parameters: mtDNA-CN decreased with increasing number of metabolic syndrome components. Furthermore, individuals with low mtDNA-CN had significantly higher odds of metabolic syndrome (OR = 1.025; 95% CI = 1.011-1.039, P = 3.19 × 10 Our data show an inverse association of mtDNA-CN with higher risk of metabolic syndrome and type 2 diabetes. A major part of the total effect of mtDNA-CN on type 2 diabetes is mediated by obesity parameters.

Sections du résumé

BACKGROUND
Mitochondria play an important role in cellular metabolism, and their dysfunction is postulated to be involved in metabolic disturbances. Mitochondrial DNA is present in multiple copies per cell. The quantification of mitochondrial DNA copy number (mtDNA-CN) might be used to assess mitochondrial dysfunction.
OBJECTIVES
We aimed to investigate the cross-sectional association of mtDNA-CN with type 2 diabetes and the potential mediating role of metabolic syndrome.
METHODS
We examined 4812 patients from the German Chronic Kidney Disease (GCKD) study and 9364 individuals from the Cooperative Health Research in South Tyrol (CHRIS) study. MtDNA-CN was measured in whole blood using a plasmid-normalized qPCR-based assay.
RESULTS
In both studies, mtDNA-CN showed a significant correlation with most metabolic syndrome parameters: mtDNA-CN decreased with increasing number of metabolic syndrome components. Furthermore, individuals with low mtDNA-CN had significantly higher odds of metabolic syndrome (OR = 1.025; 95% CI = 1.011-1.039, P = 3.19 × 10
CONCLUSIONS
Our data show an inverse association of mtDNA-CN with higher risk of metabolic syndrome and type 2 diabetes. A major part of the total effect of mtDNA-CN on type 2 diabetes is mediated by obesity parameters.

Identifiants

DOI: 10.1111/joim.13242 PMID: 33453124 PMC: PMC8359248
pubmed: 33453124
doi: 10.1111/joim.13242
pmc: PMC8359248
doi:

Substances chimiques

DNA, Mitochondrial 0
Triglycerides 0

Types de publication

Journal Article Multicenter Study Observational Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

190-202

Informations de copyright

© 2021 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

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Auteurs

F Fazzini (F)

From the, Department of Genetics and Pharmacology, Institute of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria.

C Lamina (C)

From the, Department of Genetics and Pharmacology, Institute of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria.

A Raftopoulou (A)

Eurac Research, Institute for Biomedicine, Affiliated Institute of the University of Lübeck, Bolzano, Italy.

A Koller (A)

From the, Department of Genetics and Pharmacology, Institute of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria.

C Fuchsberger (C)

Eurac Research, Institute for Biomedicine, Affiliated Institute of the University of Lübeck, Bolzano, Italy.

C Pattaro (C)

Eurac Research, Institute for Biomedicine, Affiliated Institute of the University of Lübeck, Bolzano, Italy.

F M Del Greco (FM)

Eurac Research, Institute for Biomedicine, Affiliated Institute of the University of Lübeck, Bolzano, Italy.

P Döttelmayer (P)

From the, Department of Genetics and Pharmacology, Institute of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria.

L Fendt (L)

From the, Department of Genetics and Pharmacology, Institute of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria.

J Fritz (J)

Department of Medical Statistics, Informatics and Health Economics, Medical University of Innsbruck, Innsbruck, Austria.
Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA.

H Meiselbach (H)

Department of Nephrology and Hypertension, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.

S Schönherr (S)

From the, Department of Genetics and Pharmacology, Institute of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria.

L Forer (L)

From the, Department of Genetics and Pharmacology, Institute of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria.

H Weissensteiner (H)

From the, Department of Genetics and Pharmacology, Institute of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria.

P P Pramstaller (PP)

Eurac Research, Institute for Biomedicine, Affiliated Institute of the University of Lübeck, Bolzano, Italy.

K-U Eckardt (KU)

Department of Nephrology and Hypertension, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany.

A A Hicks (AA)

Eurac Research, Institute for Biomedicine, Affiliated Institute of the University of Lübeck, Bolzano, Italy.

F Kronenberg (F)

From the, Department of Genetics and Pharmacology, Institute of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria.
ORCID: 0000-0003-2229-1120

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Association of mitochondrial DNA copy number...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Mesures épidémiologiques › Biométrie › Anthropométrie › Indice de masse corporelle › Association of mitochondrial DNA copy number...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études transversales › Association of mitochondrial DNA copy number...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Variation structurale du génome › Variations de nombre de copies de segment d'ADN › Association of mitochondrial DNA copy number...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ADN › ADN mitochondrial › Association of mitochondrial DNA copy number...
questionsmedicales.fr › Maladies endocriniennes › Diabète › Diabète de type 2 › Association of mitochondrial DNA copy number...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Association of mitochondrial DNA copy number...
questionsmedicales.fr › Maladies métaboliques et nutritionnelles › Maladies métaboliques › Syndrome métabolique X › Association of mitochondrial DNA copy number...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Association of mitochondrial DNA copy number...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études prospectives › Association of mitochondrial DNA copy number...
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