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

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

Nutrition and Genomics, USDA-HNRCA Tufts University, Boston, MA 02111

Corresponding Author: toshiko.tanaka{at}tufts.edu

Peroxisome proliferator-activated receptor alpha (PPARA) is a ligand-dependent transcription factor that plays a key role in lipid and glucose homeostasis. This study evaluated whether variants of PPARA are associated with postprandial lipemia. Subjects were given a single fat load comprised of 60% calories as fat, 15% as protein, and 25% as carbohydrate. Blood was drawn every hour from baseline to 6 hours, then every 2.5 hours to hour 11 to determine 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 non-coding variant c.140+5435T>C was not associated with fasting lipid concentrations but was significantly associated with decreased postprandial triglyceride and cholesterol in the small triglyceride rich lipoprotein particle. Although the minor allele carriers displayed lower mean concentrations of triglyceride and cholesterol throughout the postprandial period, the differences were most pronounced in the latter period. These data suggest that PPARA variants may modulate the risk of cardiovascular disease by influencing both fasting and postprandial lipid concentrations.

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