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

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

Arterioscler Thromb Vasc Biol

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

Published: April 2003

AI Article Synopsis

Article Abstract

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

Methods And Results: 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.

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

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Source
http://dx.doi.org/10.1161/01.ATV.0000064383.88696.24DOI Listing

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