Disease Markers

Disease Markers / 2005 / Article

Open Access

Volume 21 |Article ID 576748 | https://doi.org/10.1155/2005/576748

Marzia Fanelli, Emanuela Filippi, Federica Sentinelli, Stefano Romeo, Mara Fallarino, Raffaella Buzzetti, Frida Leonetti, Marco Giorgio Baroni, "The Gly482Ser Missense Mutation of the Peroxisome Proliferator-Activated Receptor γ Coactivator-1α (PGC-1α) Gene Associates with Reduced Insulin Sensitivity in Normal and Glucose-Intolerant Obese Subjects", Disease Markers, vol. 21, Article ID 576748, 6 pages, 2005. https://doi.org/10.1155/2005/576748

The Gly482Ser Missense Mutation of the Peroxisome Proliferator-Activated Receptor γ Coactivator-1α (PGC-1α) Gene Associates with Reduced Insulin Sensitivity in Normal and Glucose-Intolerant Obese Subjects

Received05 Jan 2006
Accepted05 Jan 2006

Abstract

Among the putative candidate genes for insulin resistance, the peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) is a transcriptional coactivator of PPARγ and α, regulating a wide range of processes involved in energy production and utilization, such as thermogenesis, liver gluconeogenesis, glucose uptake in muscle. In population studies a Gly482Ser substitution in PGC-1α has been reported to be associated with increased risk of type diabetes 2 and insulin resistance. In the present study we have analysed the association between the Gly482Ser missense mutation of the PGC-1α gene and insulin sensitivity and glucose tolerance in a population of obese non-diabetic subjects. The Gly482Ser SNPs was detected by PCR-RFLP in a cohort of 358 Caucasian obese subjects (223 with normal glucose tolerance (NGT) and 125 with impaired glucose tolerance (IGT). We observed a significant association (p < 0.007) between carriers of the Gly482Ser variant of the PGC-1α gene and insulin resistance measured by HOMAIR. Multivariate analysis confirmed that the Gly482Ser SNP was a significant (p < 0.02) determinant of decreased insulin sensitivity, independently from other well-known modulators of insulin action. In conclusion, we have found significant association between the Gly482Ser variant of the PGC-1α gene and reduced insulin sensitivity in obese subjects. This association resulted independent from all other known modulators of insulin resistance, and suggests a primary role for the PGC-1α gene on the genetic susceptibility to insulin resistance in obesity.

Copyright © 2005 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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