Genetic variation in PPARG encoding peroxisome proliferator-activated receptor gamma associated with carotid atherosclerosis

Abstract

Background and purpose: Peroxisome proliferator-activated receptor gamma is a crucial molecule in atherogenesis because it is associated with metabolic risk factors such as obesity and diabetes and also plays a key role in subcellular metabolism of arterial wall macrophage foam cells. Genetic variation in PPARG has been associated with metabolic and cardiovascular end points.

Methods: We investigated the relationship between 2 common PPARG polymorphisms, namely P12A and c.1431C>T, and carotid atherosclerosis in a sample of 161 Canadian aboriginal people. Dependent variables were carotid intima media thickness (IMT), assessed using B-mode ultrasonography, and total carotid plaque volume (TPV), assessed using 3D ultrasound.

Results: Using multivariate analysis, we found that subjects with > or =1 PPARG A12 allele had less carotid IMT than others (0.72+/-0.03 versus 0.80+/-0.02 mm; P=0.0045), with no between-genotype difference in TPV. In contrast, subjects with the PPARG c.1431T allele had greater TPV than others (124+/-18.4 versus 65.1+/-23.7 mm3; P=0.0079), with no between-genotype difference in IMT.

Conclusions: The findings show an association between PPARG genotypes and carotid arterial phenotypes, and further reflect the prevailing view that the PPARG A12 allele protects against deleterious phenotypes. Also, whereas IMT and TPV are somewhat correlated with each other, they might also represent distinct traits with discrete determinants representing different stages of atherogenesis.