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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

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 glucon...

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Detalles Bibliográficos
Autores principales: Fanelli, Marzia, Filippi, Emanuela, Sentinelli, Federica, Romeo, Stefano, Fallarino, Mara, Buzzetti, Raffaella, Leonetti, Frida, Baroni, Marco Giorgio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3851614/
https://www.ncbi.nlm.nih.gov/pubmed/16403952
http://dx.doi.org/10.1155/2005/576748
Descripción
Sumario: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 HOMA(IR). 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.