Haplotype analysis of the PPARgamma Pro12Ala and C1431T variants reveals opposing associations with body weight - PubMed (original) (raw)

Multicenter Study

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

Alex Doney et al. BMC Genet. 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.

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Figures

Figure 1

PPARG Pro12Ala and C1431T have an opposing association with BMI in a type 2 diabetic population. A. Shown are the mean BMIs of subjects with type 2 diabetes within derived haplotype, expressed as a difference in mean BMI from the common Pro-C haplotype. The standard error of the mean BMI is indicated B. The individuals with a BMI in the upper quartile of BMI (BMI > 75th centile, 33.65 kg/m2) were analysed as above.

Figure 2

PPARG Pro12Ala and C1431T also have an opposing association with BMI in non-diabetic populations. A. Shown are the mean BMIs within derived haplotype expressed as a difference in mean BMI from the common Pro-C haplotype for the combined Glasgow and Dundee non-diabetic populations. The standard error of the mean BMI is indicated. B. The individuals with a BMI in the upper quartile of the combined population (BMI > 27.9 kg/m2) were analysed as above.

Figure 3

PPARG haplotype associations are replicated in army volunteers in response to exercise. Shown is the mean change in BMI observed during basic training by haplotype.

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Haplotype analysis of the PPARgamma Pro12Ala and C1431T variants reveals opposing associations with body weight - PubMed (original) (raw)