A genetic variant in cytoskeleton motors amplifies susceptibility to leukoaraiosis in hypertensive smokers: Gene-environmental interactions behind vascular white matter demyelinization

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Abstract

One of the most frequent causes of an age-associated cognitive decline is the vascular white matter demyelinization of the brain referred to as leukoaraiosis (LA). The wide range of severity of the cognitive decline caused by LA can have numerous deleterious effects on the quality of life, leading overall to far-reaching public health problems. Besides clinical risk factors such as hypertension and advanced age, genetic susceptibility factors are presumed to be of great importance in the development of LA. The protein kinesin, which is the main motor protein in the trafficking system of the mitochondria, can undergo functional damage under the circumstances of chronic hypoxia. This may give rise to a slowly developing metabolic crisis in the glia cells, a phenomenon hypothesized to account for the evolution of LA. Setting out from this assumption, we examined how the kinesin light-chain 1 (KNS2) G56836C single nucleotide polymorphism in intron 13 affects the susceptibility to LA. This genetic variant was found to be associated with cognitive disturbances and neurodegeneration, and it was presumed to affect the function of kinesin. The association analysis of the above genetic variant was performed in 229 patients with LA and 264 neuroimaging alteration-free controls. The KNS2 56836CC variant increased the risk of LA 7.76-fold in hypertensive smokers as compared with those not carrying this variant. This finding may be useful in everyday clinical practice by indicating the need for stricter preventive measures in CC carriers.

Original languageEnglish
Pages (from-to)173-179
Number of pages7
JournalJournal of Molecular Neuroscience
Volume33
Issue number2
DOIs
Publication statusPublished - Oct 2007

Fingerprint

Leukoaraiosis
Kinesin
Cytoskeleton
Blood Vessels
Genes
Neuroimaging
Mitochondria
Public health
Medical problems
Polymorphism
Introns
Brain
Proteins
Nucleotides
Protein Transport
Genetic Predisposition to Disease
White Matter
Neuroglia
Single Nucleotide Polymorphism
Public Health

Keywords

  • Cytoskeleton
  • Genetic variants
  • Kinesin
  • Leukoaraiosis
  • White matter damage

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry
  • Genetics

Cite this

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title = "A genetic variant in cytoskeleton motors amplifies susceptibility to leukoaraiosis in hypertensive smokers: Gene-environmental interactions behind vascular white matter demyelinization",
abstract = "One of the most frequent causes of an age-associated cognitive decline is the vascular white matter demyelinization of the brain referred to as leukoaraiosis (LA). The wide range of severity of the cognitive decline caused by LA can have numerous deleterious effects on the quality of life, leading overall to far-reaching public health problems. Besides clinical risk factors such as hypertension and advanced age, genetic susceptibility factors are presumed to be of great importance in the development of LA. The protein kinesin, which is the main motor protein in the trafficking system of the mitochondria, can undergo functional damage under the circumstances of chronic hypoxia. This may give rise to a slowly developing metabolic crisis in the glia cells, a phenomenon hypothesized to account for the evolution of LA. Setting out from this assumption, we examined how the kinesin light-chain 1 (KNS2) G56836C single nucleotide polymorphism in intron 13 affects the susceptibility to LA. This genetic variant was found to be associated with cognitive disturbances and neurodegeneration, and it was presumed to affect the function of kinesin. The association analysis of the above genetic variant was performed in 229 patients with LA and 264 neuroimaging alteration-free controls. The KNS2 56836CC variant increased the risk of LA 7.76-fold in hypertensive smokers as compared with those not carrying this variant. This finding may be useful in everyday clinical practice by indicating the need for stricter preventive measures in CC carriers.",
keywords = "Cytoskeleton, Genetic variants, Kinesin, Leukoaraiosis, White matter damage",
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AU - Mándi, Y.

AU - Somogyvári, F.

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