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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
IOS Press
2005
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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 |
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author | Fanelli, Marzia Filippi, Emanuela Sentinelli, Federica Romeo, Stefano Fallarino, Mara Buzzetti, Raffaella Leonetti, Frida Baroni, Marco Giorgio |
author_facet | Fanelli, Marzia Filippi, Emanuela Sentinelli, Federica Romeo, Stefano Fallarino, Mara Buzzetti, Raffaella Leonetti, Frida Baroni, Marco Giorgio |
author_sort | Fanelli, Marzia |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3851614 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2005 |
publisher | IOS Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-38516142014-08-26 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 Fanelli, Marzia Filippi, Emanuela Sentinelli, Federica Romeo, Stefano Fallarino, Mara Buzzetti, Raffaella Leonetti, Frida Baroni, Marco Giorgio Dis Markers Other 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. IOS Press 2005 2006-01-05 /pmc/articles/PMC3851614/ /pubmed/16403952 http://dx.doi.org/10.1155/2005/576748 Text en Copyright © 2005 Hindawi Publishing Corporation. |
spellingShingle | Other Fanelli, Marzia Filippi, Emanuela Sentinelli, Federica Romeo, Stefano Fallarino, Mara Buzzetti, Raffaella Leonetti, Frida Baroni, Marco Giorgio 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Other |
url | 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 |
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