Open AccessGenetic Variation in PPARG Encoding Peroxisome Proliferator-Activated Receptor γ Associated With Carotid Atherosclerosis
Author(s) -
Khalid Z. Alshali,
Andrew A. House,
Anthony J. Hanley,
Hafiz Khan,
Stewart B. Harris,
Bernard Zinman,
Mary Mamakeesick,
Aaron Fenster,
J. David Spence,
Robert A. Hegele
Publication year - 2004
Publication title -
stroke
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.397
H-Index - 319
eISSN - 1524-4628
pISSN - 0039-2499
DOI - 10.1161/01.str.0000138784.68159.a5
Subject(s) - peroxisome proliferator activated receptor gamma , genotype , medicine , allele , endocrinology , receptor , obesity , phenotype , peroxisome proliferator activated receptor , genetics , biology , gene
Background and Purpose— Peroxisome proliferator-activated receptor γ 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 inPPARG has been associated with metabolic and cardiovascular end points.Methods— We investigated the relationship between 2 commonPPARG 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 ≥1PPARG 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 thePPARG 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 betweenPPARG genotypes and carotid arterial phenotypes, and further reflect the prevailing view that thePPARG 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.