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- Title
Haplotype analysis of the PPARγ Pro12Ala and C1431T variants reveals opposing associations with body weight.
- Authors
Doney, Alex; Fischer, Bettina; Frew, David; Cumming, Alastair; Flavell, David M.; World, Michael; Montgomery, Hugh E.; Boyle, Douglas; Morris, Andrew; Palmer, Colin N. A.
- 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.
- Subjects
BODY weight; BIOLOGICAL variation; TYPE 2 diabetes; GENETIC polymorphisms; BODY mass index
- Publication
BMC Genetics, 2002, Vol 3, p21
- ISSN
1471-2156
- Publication type
Article
- DOI
10.1186/1471-2156-3-21