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Background: Several perilipin (PLIN) polymorphic sites have been studied for their potential use as markers for obesity and the metabolic syndrome., Objective: We aimed to examine whether the presence of polymorphisms at the perilipin (PLIN) locus (PLIN1, 6209T-->C; PLIN4, 11482G-->A; PLIN5, 13041A-->G; and PLIN6, 14995A-->T) influence postprandial lipoprotein metabolism in 2 white populations., Design: Eighty-eight healthy Spanish men and 271 healthy US subjects (men and women) underwent an oral-fat-load test in 2 independent studies. Blood samples were taken in the fasting state and during the postprandial phase at regular intervals. Total cholesterol and triacylglycerol and triacylglycerol in triacylglycerol-rich lipoproteins (TRL, large and small) were measured., Results: Carriers of the minor C allele at the PLIN1 variant displayed lower postprandial concentrations of large-TRL triacylglycerol (Spanish subjects: P = 0.024; US subjects: P = 0.005) than did subjects carrying the T/T genotype. The same pattern was observed in the Spanish population at the PLIN4 locus (P = 0.015), and both SNPs were in strong linkage disequilibrium. In both populations, subjects carrying the minor C and A alleles at PLIN1 and PLIN4, respectively, had significantly lower postprandial concentrations of plasma triacylglycerol (P < 0.05) and lower concentrations of small-TRL triacylglycerol than did those who were homozygous for the major alleles at PLIN1 and PLIN4 (Spanish subjects: P = 0.020 and 0.008, respectively; US subjects: P = 0.021 and 0.035, respectively)., Conclusion: These 2 studies suggest that the presence of the minor C and A alleles at PLIN1 and PLIN4, respectively, are associated with a lower postprandial response that may result in lower atherogenic risk for these persons.