Peroxisome Proliferator-Activated Receptors (PPARs) and its co-activators are regulatory elements of the cellular lipid homeostasis and have been associated with feeding behavior modulation. Animal models suggest that these genes may be involved in alcohol consumption regulation. However, no studies in humans exist. Our aim is to estimate the possible association between polymorphisms in the PPAR-alpha, PPAR-gamma and PPAR-gamma co-activator 1A (PGC-1A) genes and alcohol consumption in humans.We have conducted a cross-sectional study between the PPAR-alpha L162V, PPAR-gamma P12A and PGC-1A G482S polymorphisms, and alcohol consumption in a general Mediterranean Spanish population (303 men and 443 women).We have found an association between the L162V polymorphism and alcohol consumption in which, carriers of the V allele were more prevalent among alcohol consumers (19.4% vs. 9.8%; OR 2.69; 95% CI: 1.31-5.54, p=0.007). The G482S polymorphism showed a significantly higher frequency in the group of high alcohol drinkers than in non-high alcohol drinkers (33.4% vs. 20.6%; OR 2.28; 95% CI: 1.07-4.88, p=0.034). Mean alcohol consumption was higher as the number of G alleles increased (GG 8.6+/-12.8 g/day, GS 6.6+/-9.2 g/day, SS 5.6+/-7.8 g/day, p=0.003). These results remained statistically significant after covariate adjustment.PPAR-alpha L162V and PGC-1A G482S polymorphisms are associated with alcohol consumption in the Mediterranean population.