Document Detail


A functional variant in the peroxisome proliferator-activated receptor gamma2 promoter is associated with predictors of obesity and type 2 diabetes in Pima Indians.
MedLine Citation:
PMID:  12829658     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Peroxisome proliferator-activated receptor gamma (PPARgamma)-2 is a member of the nuclear hormone receptor superfamily that is expressed predominantly in adipocytes and is thought to have a role in energy homeostasis, adipogenesis, and insulin sensitivity. A functional single nucleotide polymorphism (SNP) that predicts a proline to alanine substitution (Pro12Ala) within the coding region of this gene has previously been associated with obesity and type 2 diabetes in several populations. In this study, we identified several novel SNPs in the promoter region of PPARgamma2 and genotyped them, along with the previously identified Pro12Ala SNP. In 241 nondiabetic Pima subjects, the Pro12Ala was associated with whole-body insulin action (P = 0.05), hepatic insulin action (P = 0.03), and fasting plasma insulin concentrations (P = 0.01). One of the promoter SNPs positioned within a putative E2 box was in high linkage disequilibrium (/D'/ = 0.98) with the Pro12Ala. This promoter SNP was similarly associated with whole-body insulin action (P = 0.04) and hepatic insulin action (P = 0.05), but not fasting plasma insulin concentrations. Functional studies in transfected 3T3-L1 cells demonstrated that this single base substitution in the putative E2 box significantly altered transcriptional activity from a luciferase reporter construct. These data indicate that this promoter SNP, via its effect on PPARgamma2 expression, may also have functional consequences on PPARgamma2-activated pathways, and perhaps both the promoter SNP and the Pro12Ala contribute to PPARgamma2-related phenotypes.
Authors:
Yunhua Li Muller; Clifton Bogardus; Brock A Beamer; Alan R Shuldiner; Leslie J Baier
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Diabetes     Volume:  52     ISSN:  0012-1797     ISO Abbreviation:  Diabetes     Publication Date:  2003 Jul 
Date Detail:
Created Date:  2003-06-27     Completed Date:  2003-08-19     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0372763     Medline TA:  Diabetes     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1864-71     Citation Subset:  AIM; IM    
Affiliation:
Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Phoenix, Arizona 85016, USA.
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MeSH Terms
Descriptor/Qualifier:
3T3 Cells
Adult
Animals
Arizona
Blood Glucose / metabolism
Diabetes Mellitus / genetics*
Diabetes Mellitus, Type 2 / genetics*
Genes, Reporter
Genetic Variation*
Humans
Indians, North American / genetics*
Insulin / blood
Longitudinal Studies
Luciferases / genetics
Mice
Obesity / genetics*
Polymorphism, Single Nucleotide*
Predictive Value of Tests
Promoter Regions, Genetic*
Receptors, Cytoplasmic and Nuclear / genetics*
Transcription Factors / genetics*
Transfection
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/Receptors, Cytoplasmic and Nuclear; 0/Transcription Factors; 11061-68-0/Insulin; EC 1.13.12.-/Luciferases

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