Postprandial Triglyceride Metabolism is Modified by the Presence of Genetic Variation at the Perilipin (PLIN) Locus in Two Caucasian Populations

Authors: PEREZ-MARTINEZ, PABLO - JM USDA HNRCA @ TUFTS; YIANNAKOURIS, NIKOS - JM USDA HNRCA @ TUFTS; LOPEZ MIRANDA, JOSE - REINA SOFIA UNIN, SPAIN; ARNETT, DONNA - UNIV OF ALABAMA, BIRM; TSAI, MICHAEL - UNIV OF MINN, MINNEAPOLIS; GALAN, ENRIQUE - REINA SOFIA UNIN, SPAIN; STRAKA, ROBERT - UNIV OF MINN, MINNEAPOLIS; DELGADO-LISTA, JAVIER - REINA SOFIA UNIN, SPAIN; PROVINCE, MICHAEL - WASHINGTON UNIV, MISSOURI; RUANO, JUAN - REINA SOFIA UNIN, SPAIN; BORECKI, INGRID - WASHINGTON UNIV, MISSOURI; HIXSON, JAMES - UNIV OF TX, HOUSTON; GARCIA-BAILO, BIBIANA - JM USDA HNRCA @ TUFTS; PEREZ-JIMENEZ, FRANCISCO - REINA SOFIA UNIN, SPAIN; Ordovas, Jose

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/8/2007
Publication Date: 3/1/2008
Citation: Perez-Martinez, P., Yiannakouris, N., Lopez Miranda, J., Arnett, D., Tsai, M., Galan, E., Straka, R., Delgado-Lista, J., Province, M., Ruano, J., Borecki, I., Hixson, J., Garcia-Bailo, B., Perez-Jimenez, F., Ordovas, J.M. 2008. Postprandial Triglyceride Metabolism is Modified by the Presence of Genetic Variation at the Perilipin (PLIN) Locus in Two Caucasian Populations. American Journal of Clinical Nutrition. 87(3):744-752.

Interpretive Summary: Perilipin is one of the most abundant proteins found in fat cells. Previously, we have examined several common genetic polymorphism in the perilipin gene to learn if they were predictor of obesity and response to diet therapy to reduce body weight. Our research has shown that this gene is, indeed, associated with body weight, especially in women. Moreover, we have demonstrated that this gene was also involved in the risk of insulin resistance resulting from consumption of saturated fat. Both, obesity and insulin resistance, along with dyslipidemia and hypertension, are associated with the Metabolic Syndrome, a common cardiovascular disease risk characterized by the co-occurrence of the above mentioned risk factors. Therefore, we decided to examine whether the perilipin gene was also associated with dyslipidemia, and more specifically, the one occurring in the fed state. For this purpose we investigated two populations: 88 healthy Spanish men and 271 US subjects from the general population, who consumed fat-rich meals. Our data demonstrate that in both studies, the presence of certain common genetic polymorphisms within the perilipin gene was associated with a higher postprandial lipid and therefore an increased cardiovascular disease risk. These body of work will contribute to better characterization of individuals at high risk and will facilitate more targeted and successful dietary recommendations.

Technical Abstract: Background: Several perilipin (PLIN) polymorphic sites have 1 been studied for their potential use as markers for obesity and the metabolic syndrome. Objective: to examine whether the presence of several polymorphisms at the perilipin (PLIN) locus (PLIN1: 6209T>C, PLIN4:11482G>A, PLIN5: 13041A>G, and PLIN6: 14995A>T) influence postprandial lipoprotein metabolism in two different Caucasian populations. Design: 88 healthy Spanish men and 271 US subjects from the general population underwent an oral fat-load test in two independent studies. Blood samples were taken at regular intervals. Total cholesterol and triacylglycerols (TAGs), and TAGs in triacylglycerol-rich lipoproteins (TRL) (large and small triacylglycerol-rich lipoproteins) were determined. Results: Subjects carrying the T/T genotype at the PLIN1 displayed greater postprandial concentrations of large-TRL TAGs (Spanish subjects: P=0.024 and US subjects: P=0.005) than did carriers of the minor allele C (T/C and C/C). The same behavior was observed in the Spanish population at the PLIN4 variant (P=0.015). In both groups, individuals carrying the T/T and G/G genotypes at the PLIN1 and PLIN4 respectively had significantly higher postprandial concentrations of plasma TAGs (P<0.05) and also displayed greater concentrations of small TRL TAGs than did carriers of the minor alleles C and A (Spanish: P=0.020 and P=0.008, respectively; US: P=0.021 and P=0.035, respectively). Conclusions: These two studies suggest that the presence of the genotypes T/T and G/G at the PLIN1 and PLIN4 respectively are associated with a higher postprandial response and may partly explain the large interindividual differences in postprandial lipemic response.