Literature DB >> 10440134

Homozygosity of the Pro12Ala variant of the peroxisome proliferation-activated receptor-gamma2 (PPAR-gamma2): divergent modulating effects on body mass index in obese and lean Caucasian men.

J Ek1, S A Urhammer, T I Sørensen, T Andersen, J Auwerx, O Pedersen.   

Abstract

AIMS/HYPOTHESIS: The objectives of the present investigation were to examine: 1) whether a Pro115Gln variant in the peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) is associated with juvenile-onset obesity among Danish Caucasianmen and 2) whether the relation of a Pro12Ala polymorphism in PPAR-gamma2 with BMI and long-term weight regulation differ between lean and obese subjects within the same cohort.
METHODS: The Pro115Gln and Pro112Ala variants were examined using PCR and RFLP in a group of 752 subjects with a Body Mass Index (BMI) of 31.0 kg/m2 or more and in 869 non-obese control subjects.
RESULTS: We did not find Pro115Gln in any of the 1621 male subjects we examined. Among the males with juvenile-onset obesity, the allelic frequency of the Pro12Ala polymorphism was 14% (95% confidence interval: 12-16%) compared with 16% (14-17%) among the non-obese control subjects (NS). Heterozygosity of the codon 12 variant was not associated with differences in BMI or changes in body weight regulation during follow up in lean or obese subjects. In the group of obese subjects, 21 homozygous Ala12Ala carriers had, however, a higher BMI (38.9 +/- 5.4 kg/m2 (means +/- SD) vs 35.5 +/- 5.5 kg/ m2, p = 0.008) and a higher weight gain (0.27 +/- 0.24 kg x m(-2) x year(-1) vs 0.10 +/- 0.24 kg x m(-2) x year(-1), p = 0.004), compared with wild-type carriers. Moreover, within the control group of 869 men the 14 homozygous carriers of the variant had a lower BMI (24.4 +/- 2.7 kg/m2 vs 26.2 +/- 3.7 kg/m2, p = 0.005) and a slower increase in BMI (0.11 +/- 0.11 kg x m(-2) x year(-1) vs 0.17 +/- 0.11 kg x m(-2) x year(-1), p = 0.002) compared with wild-type carriers. CONCLUSION/
INTERPRETATION: The codon 12 variant of PPAR-gamma2 is not intrinsically associated with juvenile obesity. The variant may in its homozygous form interact, however, with various combinations of genetic and environmental factors in lean and obese subjects to cause divergent modulating effects on BMI and long-term body weight control.

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Year:  1999        PMID: 10440134     DOI: 10.1007/s001250051243

Source DB:  PubMed          Journal:  Diabetologia        ISSN: 0012-186X            Impact factor:   10.122


  30 in total

1.  No interactions between polymorphisms in the beta3-adrenergic receptor gene and the PPAR-gamma gene on the risk of the insulin resistance syndrome in the Danish MONICA cohort.

Authors:  L Frederiksen; K Brødbaek; M Fenger; S Madsbad; S A Urhammer; T Jørgensen; K Borch-Johnsen
Journal:  Diabetologia       Date:  2003-05-09       Impact factor: 10.122

2.  Frequency and significance of Pro12Ala and Pro115Gln polymorphism in gene for peroxisome proliferation-activated receptor-gamma regarding metabolic parameters in a Caucasian cohort.

Authors:  A Schäffler; N Barth; G Schmitz; B Zietz; K D Palitzsch; J Schölmerich
Journal:  Endocrine       Date:  2001-04       Impact factor: 3.633

3.  The clinical biochemistry of obesity.

Authors:  Ken A Sikaris
Journal:  Clin Biochem Rev       Date:  2004-08

4.  Amerindians show no association of PPAR-γ2 gene Ala12 allele and obesity: an "unthrifty" variant population genetics.

Authors:  Antonio Arnaiz-Villena; Mercedes Fernández-Honrado; Cristina Areces; Mercedes Enríquez-de-Salamanca; Sedeka Abd-El-Fatah-Khalil; Carmen Coca; Ignacio Arribas; Manuel Algora; Diego Rey
Journal:  Mol Biol Rep       Date:  2012-10-25       Impact factor: 2.316

5.  PPAR-gamma Pro12Ala genotype and risk of cognitive decline in elders.

Authors:  K Yaffe; A M Kanaya; K Lindquist; W C Hsueh; S R Cummings; B Beamer; A Newman; C Rosano; R Li; T Harris
Journal:  Neurobiol Aging       Date:  2006-10-18       Impact factor: 4.673

6.  Patterns of association between PPARgamma genetic variation and indices of adiposity and insulin action in African-Americans and whites: the CARDIA Study.

Authors:  Qi Wei; David R Jacobs; Pamela J Schreiner; David S Siscovick; Michael W Steffes; Myriam Fornage
Journal:  J Mol Med (Berl)       Date:  2006-09-06       Impact factor: 4.599

Review 7.  The role of peroxisome proliferator-activated receptor gamma in diabetes and obesity.

Authors:  Francesco S Celi; Alan R Shuldiner
Journal:  Curr Diab Rep       Date:  2002-04       Impact factor: 4.810

Review 8.  Genetics of insulin resistance.

Authors:  Maria M Mercado; John C McLenithan; Kristi D Silver; Alan R Shuldiner
Journal:  Curr Diab Rep       Date:  2002-02       Impact factor: 4.810

Review 9.  PPARgamma in human and mouse physiology.

Authors:  Sami Heikkinen; Johan Auwerx; Carmen A Argmann
Journal:  Biochim Biophys Acta       Date:  2007-03-27

Review 10.  Peroxisome proliferator-activated receptor gamma (PPargamma) as a novel target for prostate cancer.

Authors:  Matthew R Smith; Philip W Kantoff
Journal:  Invest New Drugs       Date:  2002-05       Impact factor: 3.850

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