Haplotype analysis of the PPARγ Prol 12Ala and CI431T variants reveals opposing associations with body weight

TY - JOUR

T1 - Haplotype analysis of the PPARγ Prol 12Ala and CI431T variants reveals opposing associations with body weight

AU - Doney, Alex

AU - Fischer, Bettina

AU - Frew, David

AU - Cumming, Alastair

AU - Flavell, David M.

AU - World, Michael

AU - Montgomery, Hugh E.

AU - Boyle, Douglas

AU - Morris, Andrew

AU - Palmer, Colin N.A.

PY - 2002/11/13

Y1 - 2002/11/13

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/0037073439

U2 - 10.1186/1471-2156-3-21

DO - 10.1186/1471-2156-3-21

M3 - Article

C2 - 12429071

AN - SCOPUS:0037073439

SN - 1471-2156

VL - 3

JO - BMC Genetics

JF - BMC Genetics

M1 - 21

ER -