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Arterioscler Thromb Vasc Biol. 2003 Apr 1;23(4):637-43. Epub 2003 Feb 27.

Evidence that peroxisome proliferator-activated receptor delta influences cholesterol metabolism in men.

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Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Hospital, SE-171 76 Stockholm, Sweden.



The objective of this work was to explore the role of peroxisome proliferator-activated receptor delta (PPARD) in lipid metabolism in humans.


PPARD is a nuclear receptor involved in lipid metabolism in primates and mice. We screened the 5'-region of the human gene for polymorphisms to be used as tools in association studies. Four polymorphisms were detected: -409C/T in the promoter region, +73C/T in exon 1, +255A/G in exon 3, and +294T/C in exon 4. The frequencies of the rare alleles were 4.2%, 4.2%, 1.2% and 15.6%, respectively, in a population-based group of 543 healthy men. Only the +294T/C polymorphism showed significant association with a metabolic trait. Homozygotes for the rare C allele had a higher plasma LDL-cholesterol concentration than homozygotes for the common T allele, which was verified in an independent cohort consisting of 282 healthy men. Transfection studies showed that the rare C allele had higher transcriptional activity than the common T allele. Electrophoretic mobility shift assays demonstrated that the +294T/C polymorphism influenced binding of Sp-1. An interaction with the PPAR alpha L162V polymorphism was also detected for several lipid parameters.


These findings suggest that PPARD plays a role in cholesterol metabolism in humans.

[Indexed for MEDLINE]

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