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Open Access Highly Accessed Research article

Haplotype analysis of the PPARγ Pro12Ala and C1431T variants reveals opposing associations with body weight

Alex Doney123, Bettina Fischer1, David Frew1, Alastair Cumming4, David M Flavell5, Michael World6, Hugh E Montgomery5, Douglas Boyle3, Andrew Morris2 and Colin NA Palmer1*

Author Affiliations

1 Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY. Scotland, United Kingdom

2 Department of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY. Scotland, United Kingdom

3 Medicines Monitoring Unit, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY. Scotland, United Kingdom

4 Department of Molecular and Cell Biology, University of Aberdeen, Aberdeen, AB25 2ZN, Scotland, United Kingdom

5 Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Rayne Building, Department of Medicine, Royal Free and University College London, 5 University St., London WC1E 6JJ, England, United Kingdom

6 Centre for Defence Medicine HQ, Selly Oak Hospital, Raddlebarn Road, Birmingham B29 6JD, England, United Kingdom

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BMC Genetics 2002, 3:21  doi:10.1186/1471-2156-3-21

Published: 13 November 2002

Abstract

Background

Variation at the PPARG locus may influence susceptibility to type 2 diabetes and related traits. The Pro12Ala polymorphism may modulate receptor activity and is associated with protection from type 2 diabetes. However, there have been inconsistent reports of its association with obesity. The silent C1431T polymorphism has not been as extensively studied, but the rare T allele has also been inconsistently linked to increases in weight. Both rare alleles are in linkage disequilibrium and the independent associations of these two polymorphisms have not been addressed.

Results

We have genotyped a large population with type 2 diabetes (n = 1107), two populations of non-diabetics from Glasgow (n = 186) and Dundee (n = 254) and also a healthy group undergoing physical training (n = 148) and investigated the association of genotype with body mass index. This analysis has demonstrated that the Ala12 and T1431 alleles are present together in approximately 70% of the carriers. By considering the other 30% of individuals with haplotypes that only carry one of these polymorphisms, we have demonstrated that the Ala12 allele is consistently associated with a lower BMI, whilst the T1431 allele is consistently associated with higher BMI.

Conclusion

This study has therefore revealed an opposing interaction of these polymorphisms, which may help to explain previous inconsistencies in the association of PPARG polymorphisms and body weight.