T16189C mitochondrial DNA variant is associated with metabolic syndrome in Caucasian subjects.
ABSTRACT Different nuclear genes are thought to be involved in the regulation of the complex phenotype of metabolic syndrome (MS) and their number is increasing. A mutation in mitochondrial DNA (mtDNA), T4291C in transfer RNA isoleucine (tRNAile), has been associated with MS in a large American family. In addition, a mtDNA T16189C variant, already known to be associated with insulin resistance and type 2 diabetes mellitus in Caucasians, seems to underlie susceptibility to MS in the Chinese population. Our aim was to verify the T4291C and T16189C variants in subjects affected by different phenotypes of MS.
Seventy patients with MS and 35 healthy individuals were investigated for the presence of the mtDNA variants by polymerase chain reaction-restriction fragment length polymorphism analysis.
The T4291C variant was absent in patients and in controls. The T16189C variant was more frequent in patients with MS than in control subjects (21.4% versus 5.7%, P<0.04) and was associated with hypertension (P=0.01), waist circumference (P=0.02), body mass index (P=0.009), visceral fat thickness (P=0.04), homeostasis model assessment (P=0.03), and the number of MS diagnostic criteria (P=0.01).
The mtDNA T16189C variant is associated with MS and its different clinical expressions. Prospective studies are warranted to establish the clinical relevance of this association.
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ABSTRACT: Persistent organic pollutants (POPs) are known to cause mitochondrial dysfunction and this in turn is linked to insulin resistance, a key biochemical abnormality underlying the metabolic syndrome. To establish the cause and effect relationship between exposure to POPs and the development of the metabolic syndrome, Koch's postulates were considered. Problems arising from this approach were discussed and possible solutions were suggested. In particular, the difficulty of establishing a cause and effect relationship due to the vagueness of the metabolic syndrome as a disease entity was discussed. Recently a bioassay, aryl-hydrocarbon receptor (AhR) trans-activation activity using a cell line expressing AhR-luciferase, showed that its activity is linearly related with the parameters of the metabolic syndrome in a population. This finding suggests the possible role of bioassays in the analysis of multiple pollutants of similar kinds in the pathogenesis of several closely related diseases, such as type 2 diabetes and the metabolic syndrome. Understanding the effects of POPs on mitochondrial function will be very useful in understanding the integration of various factors involved in this process, such as genes, fetal malnutrition and environmental toxins and their protectors, as mitochondria act as a unit according to the metabolic scaling law.Diabetes & metabolism journal 06/2011; 35(3):207-15.