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

A Doney, B Fischer, D Frew, A Cumming, D M Flavell, M World, H E Montgomery, D Boyle, A Morris, C N A Palmer

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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.
Original languageEnglish
Article number21
Number of pages8
JournalBMC Genetics
Volume3
DOIs
Publication statusPublished - 13 Nov 2002

Keywords

  • proliferator-activated-receptor
  • plasma leptin levels
  • insulin sensitivity
  • obese subjects
  • mass index
  • combined hyperlipidemia
  • receptor-gamma(2) gene
  • diabetes-mellitus
  • missense mutation
  • PPAR-gamma-2 gene

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    Doney, A., Fischer, B., Frew, D., Cumming, A., Flavell, D. M., World, M., Montgomery, H. E., Boyle, D., Morris, A., & Palmer, C. N. A. (2002). Haplotype analysis of the PPAR gamma Pro12Ala and C1431T variants reveals opposing associations with body weight. BMC Genetics, 3, [21]. https://doi.org/10.1186/1471-2156-3-21