© 1999 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Peroxisome Proliferator–Activated Receptor 
Gene Locus Is Related to Body Mass Index and Lipid Values in Healthy Nonobese Subjects
From the Franz Volhard Clinic and Max Delbrück Center for Molecular Medicine (H.K., A.B., H.-D.F., H.S., R.U., F.C.L.), Charité, Medical Faculty of the Humboldt University of Berlin, Berlin; and Bernhard Nocht Institute for Tropical Medicine (B.M.-M.), Department of Molecular Medicine, Hamburg, Germany.
Correspondence to Friedrich C. Luft, Franz Volhard Clinic, Wiltbergstrasse 50, 13122 Berlin, Germany. E-mail: luft{at}fvk-berlin.de
Abstract—The peroxisome
proliferator–activated receptor 
(PPAR)
gene has been implicated in morbid obesity and is important to lipid
and carbohydrate metabolism. However, the relevance of gene
variations in healthy nonobese subjects has not been defined. We
recruited monozygotic and dizygotic healthy nonobese twin subjects to
test the hypothesis that the PPAR gene is important
to body mass index and lipid concentrations in healthy nonobese
subjects. Both linkage and association strategies were used in the same
dizygotic twins. The PPAR gene locus was linked
(P<0.01) to high-density lipoprotein
cholesterol, low-density lipoprotein
cholesterol, and body mass index as quantitative traits. A
biallelic variant in the PPAR gene was associated
with high-density lipoprotein cholesterol and body mass
index (P<0.05). We also looked for linkage between the
same variables and the retinoic X receptor gene locus. This locus
was linked to total and low-density lipoprotein cholesterol
as well as triglycerides. We conclude that the
PPAR gene is highly relevant to lipid
metabolism and body mass index, not only in the morbidly
obese but also in healthy nonobese subjects. The same appears to be
true for its binding partner. Sequencing these genes in twins would
serve to identify gene variations contributing to body mass index and
lipid concentrations in healthy nonobese subjects.
Key Words: genetics • PPAR • quantitative trait loci • body mass index • cholesterol, HDL • cholesterol, LDL • twins
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