Omega-3 fatty acids regulate gene expression levels differently in subjects carrying the PPARalpha L162V polymorphism

Omega-3 fatty acids (FAs) are natural ligands of the peroxisome proliferator-activated receptor-alpha (PPARalpha), a nuclear receptor that modulates expression levels of genes involved in lipid metabolism. The L162V polymorphism of the PPARalpha gene is associated with a deteriorated metabolic profile. We postulate that subjects carrying the PPARalpha-V162 allele exhibit differences in the expression of PPARalpha and its target genes after incubation with omega-3 FAs compared with L162 homozygotes. Peripheral blood monocytes from six men carrying the PPARalpha-V162 allele paired for age and for body mass index with six L162 homozygotes were differentiated into macrophages and activated with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or mixtures of EPA:DHA. Data demonstrates that gene expression levels of PPARalpha and apolipoprotein AI (APOA1) were significantly lower for carriers of the PPARalpha-V162 allele compared to L162 homozygotes after the addition of DHA and a mixture of EPA:DHA. Additionally, lipoprotein lipase (LPL) gene expression displayed a tendency to be lower in the PPARalpha L162V polymorphism subgroup after the addition of a mixture of EPA:DHA. Consequently, individuals carrying the PPARalpha-V162 allele may demonstrate inferior improvements in their lipid profile due to alterations in gene expression rates in response to omega-3 FA supplementation.