A homozygous genetic variant of mitochondrial uncoupling protein 4 exerts protection against the occurrence of multiple sclerosis

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13 Citations (Scopus)

Abstract

Multiple sclerosis (MS), which results in damage of the white matter at multiple foci, poses a far-reaching public health problem in view of the burden it imposes on the affected young and middle-aged. Some previous data suggested that roles could be played in the demyelinization of the white matter of the brain by the malfunctioning of the mitochondria and mitochondria-associated reactive oxygen species. In this context, we hypothesized that the finely tuned dynamic stability of the mitochondrial membrane potential (MMP), which is the main mirror of the functional state of the mitochondria, is essential for the intact nature of the glia cells in the brain. Setting out from this, our aim in this study was to examine how the rs10807344 and rs2270450 genetic variants of mitochondrial uncoupling protein 4 (mUCP4) can give rise to the development of MS, since mUCP4 is presumed to be of great importance in the regulation of the MMP and cellular energy metabolism. The clinical and genetic data on 120 relapsing-remitting MS patients and 250 neuroimaging alteration-free subjects were analyzed. The rs10807344 CC genotype proved to exert a protective effect against the occurrence of MS (neuroimaging alteration-free controls, 58%; MS group, 33%; P <0.0000089; OR, 0.32; 95% CI: 0.2-0.56, P <0.005). The present findings indirectly raise the possibility that a shift or imbalance in the finally regulated MMP plays a role in the development of MS.

Original languageEnglish
Pages (from-to)101-105
Number of pages5
JournalNeuroMolecular Medicine
Volume11
Issue number2
DOIs
Publication statusPublished - jún. 2009

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Multiple Sclerosis
Mitochondrial Membrane Potential
Mitochondria
Neuroimaging
Relapsing-Remitting Multiple Sclerosis
Brain
Neuroglia
Energy Metabolism
Reactive Oxygen Species
Public Health
Genotype
Uncoupling Protein 1
White Matter

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Molecular Medicine
  • Neurology

Cite this

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title = "A homozygous genetic variant of mitochondrial uncoupling protein 4 exerts protection against the occurrence of multiple sclerosis",
abstract = "Multiple sclerosis (MS), which results in damage of the white matter at multiple foci, poses a far-reaching public health problem in view of the burden it imposes on the affected young and middle-aged. Some previous data suggested that roles could be played in the demyelinization of the white matter of the brain by the malfunctioning of the mitochondria and mitochondria-associated reactive oxygen species. In this context, we hypothesized that the finely tuned dynamic stability of the mitochondrial membrane potential (MMP), which is the main mirror of the functional state of the mitochondria, is essential for the intact nature of the glia cells in the brain. Setting out from this, our aim in this study was to examine how the rs10807344 and rs2270450 genetic variants of mitochondrial uncoupling protein 4 (mUCP4) can give rise to the development of MS, since mUCP4 is presumed to be of great importance in the regulation of the MMP and cellular energy metabolism. The clinical and genetic data on 120 relapsing-remitting MS patients and 250 neuroimaging alteration-free subjects were analyzed. The rs10807344 CC genotype proved to exert a protective effect against the occurrence of MS (neuroimaging alteration-free controls, 58{\%}; MS group, 33{\%}; P <0.0000089; OR, 0.32; 95{\%} CI: 0.2-0.56, P <0.005). The present findings indirectly raise the possibility that a shift or imbalance in the finally regulated MMP plays a role in the development of MS.",
keywords = "Genetic variant, Mitochondria, Mitochondrial membrane potential, Mitochondrial uncoupling protein, Multiple sclerosis",
author = "Z. Szolnoki and A. Kondacs and Y. M{\'a}ndi and Anita Bodor and F. Somogyv{\'a}ri",
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T1 - A homozygous genetic variant of mitochondrial uncoupling protein 4 exerts protection against the occurrence of multiple sclerosis

AU - Szolnoki, Z.

AU - Kondacs, A.

AU - Mándi, Y.

AU - Bodor, Anita

AU - Somogyvári, F.

PY - 2009/6

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N2 - Multiple sclerosis (MS), which results in damage of the white matter at multiple foci, poses a far-reaching public health problem in view of the burden it imposes on the affected young and middle-aged. Some previous data suggested that roles could be played in the demyelinization of the white matter of the brain by the malfunctioning of the mitochondria and mitochondria-associated reactive oxygen species. In this context, we hypothesized that the finely tuned dynamic stability of the mitochondrial membrane potential (MMP), which is the main mirror of the functional state of the mitochondria, is essential for the intact nature of the glia cells in the brain. Setting out from this, our aim in this study was to examine how the rs10807344 and rs2270450 genetic variants of mitochondrial uncoupling protein 4 (mUCP4) can give rise to the development of MS, since mUCP4 is presumed to be of great importance in the regulation of the MMP and cellular energy metabolism. The clinical and genetic data on 120 relapsing-remitting MS patients and 250 neuroimaging alteration-free subjects were analyzed. The rs10807344 CC genotype proved to exert a protective effect against the occurrence of MS (neuroimaging alteration-free controls, 58%; MS group, 33%; P <0.0000089; OR, 0.32; 95% CI: 0.2-0.56, P <0.005). The present findings indirectly raise the possibility that a shift or imbalance in the finally regulated MMP plays a role in the development of MS.

AB - Multiple sclerosis (MS), which results in damage of the white matter at multiple foci, poses a far-reaching public health problem in view of the burden it imposes on the affected young and middle-aged. Some previous data suggested that roles could be played in the demyelinization of the white matter of the brain by the malfunctioning of the mitochondria and mitochondria-associated reactive oxygen species. In this context, we hypothesized that the finely tuned dynamic stability of the mitochondrial membrane potential (MMP), which is the main mirror of the functional state of the mitochondria, is essential for the intact nature of the glia cells in the brain. Setting out from this, our aim in this study was to examine how the rs10807344 and rs2270450 genetic variants of mitochondrial uncoupling protein 4 (mUCP4) can give rise to the development of MS, since mUCP4 is presumed to be of great importance in the regulation of the MMP and cellular energy metabolism. The clinical and genetic data on 120 relapsing-remitting MS patients and 250 neuroimaging alteration-free subjects were analyzed. The rs10807344 CC genotype proved to exert a protective effect against the occurrence of MS (neuroimaging alteration-free controls, 58%; MS group, 33%; P <0.0000089; OR, 0.32; 95% CI: 0.2-0.56, P <0.005). The present findings indirectly raise the possibility that a shift or imbalance in the finally regulated MMP plays a role in the development of MS.

KW - Genetic variant

KW - Mitochondria

KW - Mitochondrial membrane potential

KW - Mitochondrial uncoupling protein

KW - Multiple sclerosis

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