A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity.

Details

Serval ID
serval:BIB_02BF83E95440
Type
Article: article from journal or magazin.
Collection
Publications
Title
A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity.
Journal
Nature Genetics
Author(s)
Deeb S.S., Fajas L., Nemoto M., Pihlajamäki J., Mykkänen L., Kuusisto J., Laakso M., Fujimoto W., Auwerx J.
ISSN
1061-4036 (Print)
ISSN-L
1061-4036
Publication state
Published
Issued date
1998
Volume
20
Number
3
Pages
284-287
Language
english
Abstract
The peroxisome proliferator-activated receptor-gamma (PPARgamma) is a transcription factor that has a pivotal role in adipocyte differentiation and expression of adipocyte-specific genes. The PPARgamma1 and gamma2 isoforms result from alternative splicing and have ligand-dependent and -independent activation domains. PPARgamma2 has an additional 28 amino acids at its amino terminus that renders its ligand-independent activation domain 5-10-fold more effective than that of PPARgamma1. Insulin stimulates the ligand-independent activation of PPARgamma1 and gamma2 (ref. 5), however, obesity and nutritional factors only influence the expression of PPARgamma2 in human adipocytes. Here, we report that a relatively common Pro12Ala substitution in PPARgamma2 is associated with lower body mass index (BMI; P=0.027; 0.015) and improved insulin sensitivity among middle-aged and elderly Finns. A significant odds ratio (4.35, P=0.028) for the association of the Pro/Pro genotype with type 2 diabetes was observed among Japanese Americans. The PPARgamma2 Ala allele showed decreased binding affinity to the cognate promoter element and reduced ability to transactivate responsive promoters. These findings suggest that the PPARgamma2 Pro12Ala variant may contribute to the observed variability in BMI and insulin sensitivity in the general population.
Keywords
Adult, Aged, Alleles, Amino Acid Substitution, Base Sequence, Body Mass Index, DNA Primers/genetics, Diabetes Mellitus, Type 2/genetics, Female, Finland, Gene Frequency, Genetic Variation, Genotype, Humans, Insulin Resistance/genetics, Insulin Resistance/physiology, Male, Middle Aged, Promoter Regions, Genetic, Receptors, Cytoplasmic and Nuclear/genetics, Receptors, Cytoplasmic and Nuclear/metabolism, Transcription Factors/genetics, Transcription Factors/metabolism, Transcriptional Activation
Pubmed
Web of science
Create date
07/03/2013 16:11
Last modification date
20/08/2019 12:24
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