Peroxisome proliferator-activated receptor α polymorphisms and postprandial lipemia in healthy men

Toshiko Tanaka,Jose Lopez-Miranda,Jose M Ordovas,Carmen Marin,Purificacion Gomez,Pablo Perez-Martinez,Javier Delgado-Lista,Francisco Perez-Jimenez

doi:10.1194/jlr.m700066-jlr200

Abstract

Peroxisome proliferator-activated receptor alpha (PPARalpha) is a ligand-dependent transcription factor that plays a key role in lipid and glucose homeostasis. This study evaluated whether variants of PPARalpha are associated with postprandial lipemia. Subjects were given a single fat load composed of 60% calories as fat, 15% as protein, and 25% as carbohydrate. Blood was drawn every hour from baseline to 6 h, then every 2.5 h to 11 h to determine triglyceride (TG) levels. The minor allele of the nonsynonymous p.Leu162Val variant was associated with higher fasting total cholesterol, LDL-cholesterol, and apolipoprotein B. There were no significant associations with all of the postprandial parameters examined. Conversely, the noncoding variant c.140+5435T>C was not associated with fasting lipid concentrations but was significantly associated with decreased postprandial TG and cholesterol in the small TG-rich lipoprotein particle. Although the minor allele carriers displayed lower mean concentrations of TG and cholesterol throughout the postprandial period, the differences were most pronounced in the latter period. These data suggest that PPARalpha variants may modulate the risk of cardiovascular disease by influencing both fasting and postprandial lipid concentrations.

Highlights

Peroxisome proliferator-activated receptor a (PPARa) is a ligand-dependent transcription factor that plays a key role in lipid and glucose homeostasis
We examined the effect of two PPARa polymorphisms in intron 2 and exon 6 on fasting and postprandial lipid metabolism in healthy males
Allele frequencies and linkage disequilibrium The genotype frequencies for both PPARa single nucleotide polymorphism (SNP) examined in this study were in Hardy-Weinberg equilibrium (p.Leu162Val, Chi-square 5 0.309, P 5 0.579; c.14015435T.C, Chi-square 5 0.429, P 5 0.513)

Summary

SUBJECTS AND METHODS

Human subjects Fifty-nine healthy male students at the University of Cordoba responded to an advertisement and were recruited for the study. The meal provided 1 g of fat and 7 mg of cholesterol per kilogram of body weight. The total calories consumed by the subjects ranged from 825 to 1,583 kcal, depending on their weight. Lipoprotein separation Blood was collected in tubes containing EDTA to a final concentration of 0.1% EDTA. Plasma was separated from blood cells by centrifugation at 1,500 g for 15 min at 4jC. The chylomicron fraction of triglyceride-rich lipoproteins (large-TRLs) was isolated from 4 ml of plasma overlaid with 0.15 M NaCl and 1 mM EDTA (pH 7.4, d 5 1.006 g/ml) by a single ultracentrifugal spin (28,000 g, 30 min, 4jC) in a 50 type rotor (Beckman Instruments, Fullerton, CA). Lipid analysis Cholesterol and TGs in plasma and lipoprotein fractions were assayed by enzymatic procedures [15, 16]. LDL-cholesterol was calculated as the difference between the cholesterol at the bottom of the tube after ultracentrifugation at 1.019 g/ml and the HDL-cholesterol

DNA amplification and genotyping

Statistical analysis

RESULTS

DISCUSSION