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.
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 alphaL162V polymorphism was also detected for several lipid parameters. CONCLUSIONS: These findings suggest that PPARD plays a role in cholesterol metabolism in humans.
Authors: N Grarup; A Albrechtsen; J Ek; K Borch-Johnsen; T Jørgensen; O Schmitz; T Hansen; O Pedersen Journal: Diabetologia Date: 2007-04-13 Impact factor: 10.122
Authors: Teresa Coll; Emma Barroso; David Alvarez-Guardia; Lucía Serrano; Laia Salvadó; Manuel Merlos; Xavier Palomer; Manuel Vázquez-Carrera Journal: PPAR Res Date: 2010-07-27 Impact factor: 4.964
Authors: Ildus I Ahmetov; Alun G Williams; Daniil V Popov; Ekaterina V Lyubaeva; Albina M Hakimullina; Olga N Fedotovskaya; Irina A Mozhayskaya; Olga L Vinogradova; Irina V Astratenkova; Hugh E Montgomery; Viktor A Rogozkin Journal: Hum Genet Date: 2009-12 Impact factor: 4.132