Submitted on September 24, 2007
Revised on April 15, 2008
Accepted on April 15, 2008
The effect of IL6-174C/G polymorphism on postprandial triglycerides metabolism in the GOLDN study
Jian Shen, Donna K. Arnett, Pablo Pérez-Martínez, Laurence D. Parnell, Chao-Qiang Lai, James M. Peacock, James E. Hixson, Michael Y. Tsai, Robert J. Straka, Paul N. Hopkins, and José M. Ordovás
Nutrition and Genomics Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111-1524
Corresponding Author: jose.ordovas{at}tufts.edu
Chronically elevated IL-6 affects lipid and lipoprotein metabolism. Individuals genetically predisposed to higher IL-6 secretion may be at risk of dyslipidemia, especially during the postprandial phase. We investigated the effect of polymorphisms at the IL6 locus on postprandial lipemia in US Whites participating in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). Subjects were given a single fat load composed of 3% of calories as protein, 14% as carbohydrate, and 83% as fat. Blood was drawn at 0h, 3.5h and 6h to determine plasma triglycerides (TG), TG-rich lipoprotein (TRL) and lipoprotein particle size. Homozygotes (GG) and heterozygotes (CG) of the -174C/G variant displayed higher plasma IL-6 concentrations compared with major allele homozygotes (CC) (P=0.029). GG and CG showed higher fasting plasma TG (P=0.025), VLDL (P=0.04) and large VLDL (P=0.02) concentrations than CC subjects. Moreover, GG and CG subjects experienced greater postprandial response of TG (P=0.006) and TRL including chylomicrons (P=0.005), total VLDL (P=0.029) and large VLDL (P=0.017) than CC subjects. These results suggest that the functional polymorphism -174C>G at the IL6 locus determines the difference in both fasting and postprandial TG metabolism. This phenomenon could be responsible for the observed association of this genetic variant with CVD risk.
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