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(Stroke. 2004;35:2036.)
© 2004 American Heart Association, Inc.

Original Contributions

Genetic Variation in PPARG Encoding Peroxisome Proliferator-Activated Receptor Associated With Carotid Atherosclerosis

Khalid Z. Al-Shali, MBBS; Andrew A. House, MD; Anthony J.G. Hanley, PhD; Hafiz M.R. Khan, PhD; Stewart B. Harris, MD; Bernard Zinman, MD; Mary Mamakeesick, RPN; Aaron Fenster, PhD; J. David Spence, MD Robert A. Hegele, MD

From the Robarts Research Institute (K.Z.A.-S., H.M.R.K., A.F., J.D.S., R.A.H.), London, Ontario, Canada; the Department of Medicine (A.A.H.), University of Western Ontario, London, Ontario, Canada; the Department of Medicine and Samuel Lunenfeld Research Institute (A.J.G.H., B.Z.), Mount Sinai Hospital and University of Toronto, Ontario, Canada; the Thames Valley Family Practice Research Unit (S.B.H.), University of Western Ontario, London, Ontario, Canada; and the Sandy Lake Health and Diabetes Project (M.M.), Ontario, Canada.

Correspondence to Dr Robert A. Hegele, Blackburn Cardiovascular Genetics Laboratory, Robarts Research Institute, 406-100 Perth Dr, London, Ontario, Canada N6A 5K8. E-mail hegele{at}robarts.ca

Background and Purpose— Peroxisome proliferator-activated receptor 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 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.

Key Words: atherosclerosis • carotid arteries • polymorphism • ultrasonography

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