In the past few years, there has been a substantial increase in our appreciation of the importance of postprandial triglycerides (TG) as a predictor of major cardiovascular events. Elevated non-fasting triglyceride concentrations have been associated with an increased risk of cardiovascular events and death in men 1 and women.1-4
Postprandial lipid responses vary considerably among individuals,5 and this variable response is influenced by fasting triglyceride concentration, insulin resistance and genetic regulation. Many studies have reported that genetic variants of genes involved in lipid and lipoprotein metabolism are associated with heterogeneity in postprandial responses and the risk of cardiovascular disease.
The Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study provides important genetic insights into variable postprandial responses.6 The contribution of minor alleles that regulate TG metabolism (APOA5 and -1131T>C genotypes) was investigated in normolipidemic subjects after a standardized oral fat load. APOA5, a primarily hepatic synthesized protein, is extensively involved in TG-metabolism where it has been demonstrated to act as a peroxisome proliferator-activated receptor alpha response element. In primary human cell cultures and experimental animal studies , APOA5 has been shown to inhibit VLDL production7 and facilitate VLDL clearance through activation of lipoprotein lipase (LPL).8 In GOLDN, the TG-lowering and HDL-C raising effects of fenofibrate therapy were larger in APOA5 56G carriers than non-carriers. The minor allele -1131C carriers (TC + CC) had significantly higher fasting and postprandial triglyceride concentrations than non-carriers (TT), but similar HDL-C levels. Unlike subjects with the APOA5 56C>G genotypes who responded differently to fenofibrate treatment, subjects with APOA5 and 1131T>C genotype reacted similarly to fenofibrate as non-carriers.
Evaluation of minor genes regulating postprandial lipemia provides a basis for the variable postprandial responses to fenofibrate therapy. The translation of this information on risk markers requires corroboration in clinical cardiovascular outcomes trials.
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