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

BMC Genet. 2002 Nov 13;3:21. doi: 10.1186/1471-2156-3-21. Epub 2002 Nov 13.

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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alanine / genetics*
  • Alanine / physiology
  • Amino Acid Substitution / genetics
  • Amino Acid Substitution / physiology
  • Body Mass Index
  • Body Weight / genetics*
  • Body Weight / physiology
  • Cytosine / metabolism*
  • Cytosine / physiology
  • Diabetes Mellitus, Type 2 / genetics
  • Exercise / physiology
  • Female
  • Genetic Carrier Screening / methods
  • Genetic Testing / methods
  • Genetic Variation / genetics*
  • Genotype
  • Haplotypes / genetics*
  • Haplotypes / physiology
  • Humans
  • Linkage Disequilibrium / genetics
  • Male
  • Polymorphism, Genetic / genetics
  • Polymorphism, Genetic / physiology
  • Proline / genetics*
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Receptors, Cytoplasmic and Nuclear / physiology
  • Regression Analysis
  • Thymine / metabolism*
  • Thymine / physiology
  • Transcription Factors / genetics*
  • Transcription Factors / physiology

Substances

  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • Cytosine
  • Proline
  • Alanine
  • Thymine