Effect of the PPAR-Alpha L162V Polymorphism on the Cardiovascular Disease Risk Factor in Response to n-3 Polyunsaturated Fatty Acids

Background: Dietary n-3 polyunsaturated fatty acids (PUFAs) decrease the risk of cardiovascular disease (CVD). Yet, genetic variations of the gene encoding the peroxisome proliferator-activated receptor-alpha (PPAR alpha) can also modulate CVD risk factors. Since fatty acids, including n-3 PUFAs, are natural ligands of PPAR alpha, a gene-diet interaction effect could be observed. Aims: To examine whether n-3 PUFA-induced changes in CVD risk factors are influenced by the PPAR alpha L162V polymorphism. Methods: Fourteen men, carriers of the V162 allele and 14 L162 homozygotes, were matched according to age and body mass index. Subjects followed, for 8 weeks, a low-fat diet and then were supplemented daily with 5 g of fish oil for 6 weeks. Results: Baseline characteristics were similar for both genotype groups. Independently of the genotype, the supplementation was associated with a significant decrease in plasma triacylglycerol and fasting glucose concentrations, diastolic blood pressure, and with an increase in total apolipoprotein B concentrations. The extent of the decrease in plasma triacylglycerol concentrations was comparable for both genotype groups (p < 0.03). A significant genotype-by-diet interaction effect was observed for plasma C-reactive protein concentrations (p = 0.01). Conclusions:The PPAR alpha L162V polymorphism may contribute to the interindividual variability in the CVD risk factor response to n-3 PUFAs. Copyright (C)2008 S. Karger AG, Basel