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

Open Access

1 January 2002

journal article
research article
Published by Springer Nature in BMC Genomic Data

Vol. 3 (1) , 21
https://doi.org/10.1186/1471-2156-3-21

Abstract

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. 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. 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.

Keywords

This publication has 43 references indexed in Scilit:

Peroxisome Proliferator-Activated Receptor α Gene Variants Influence Progression of Coronary Atherosclerosis and Risk of Coronary Artery Disease
Circulation, 2002
Der Polymorphismus Pro12Ala im Peroxisomenproliferator-Aktivierten Rezeptor γ₂ (PPARγ₂): Betazell-Funktion und Insulinsensitivität
Deutsche Medizinische Wochenschrift (1946), 2001
The silent PPARγ exon 6 CAC^His → CAT^His polymorphism does not affect the plasma leptin levels in a collective of first degree relatives of type 2 diabetes patients from South West Germany
Experimental and Clinical Endocrinology & Diabetes, 2000
The role of PPARγ as a thrifty gene both in mice and humans
British Journal of Nutrition, 2000
The Pro12Ala substitution in the peroxisome proliferator activated receptor gamma 2 is associated with an insulin-sensitive phenotype in families with familial combined hyperlipidemia and in nondiabetic elderly subjects with dyslipidemia
Atherosclerosis, 2000
The Pro12Ala Polymorphism in PPAR γ2 May Confer Resistance to Type 2 Diabetes
Biochemical and Biophysical Research Communications, 2000
Peroxisome Proliferator–Activated Receptor γ Gene Locus Is Related to Body Mass Index and Lipid Values in Healthy Nonobese Subjects
Arteriosclerosis, Thrombosis, and Vascular Biology, 1999
Pro12Ala Missense Mutation of the Peroxisome Proliferator Activated Receptor γ and Diabetes Mellitus
Biochemical and Biophysical Research Communications, 1999
Haplotype Structure and Population Genetic Inferences from Nucleotide-Sequence Variation in Human Lipoprotein Lipase
American Journal of Human Genetics, 1998
Molecular Scanning of the Human Peroxisome Proliferator Activated Receptor γ (hPPARγ) Gene in Diabetic Caucasians: Identification of a Pro12Ala PPARγ2 Missense Mutation
Biochemical and Biophysical Research Communications, 1997