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Papers In Press, published online ahead of print August 1, 2008
J. Lipid Res., doi:10.1194/jlr.P700033-JLR200

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Journal of Lipid Research, Vol. 49, 1839-1845, August 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

Patient-Oriented and Epidemiological Research

The effect of IL6-174C/G polymorphism on postprandial triglyceride 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^1,*

^* Nutrition and Genomics Laboratory, Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA
Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL
Reina Sofia University Hospital, Lipids and Atherosclerosis Research Unit, University of Cordoba, CIBER Fisiopatologia de la Obesidad y Nutricion, Cordoba, Spain
^** Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN
^*** Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN
Human Genetics Center, University of Texas, Houston, TX
Cardiovascular Genetics, University of Utah, Salt Lake City, UT

^* This study was supported by contract 53-K06-5-10 from NIH and 58-1950-9-001 from the US Department of Agriculture (Agriculture Research Service) and by NIH Heart, Lung and Blood Institute grants U 01 HL72524, Genetic and Environmental Determinants of Triglycerides and HL54776.

The online version of this article (available at http://www.jlr.org) contains supplementary data in the form of four tables.

Published, JLR Papers in Press, April 16, 2008.

¹ To whom correspondence should be addressed. e-mail: jose.ordovas{at}tufts.edu

Chronically elevated interleukin-6 (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 genetic variants at the IL6 locus on postprandial lipemia in US Whites participating in the Genetics of Lipid Lowering Drugs and Diet Network study. 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 0 h, 3.5 h, and 6 h to determine plasma triglyceride (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 subjects showed higher fasting plasma TG (P = 0.025), VLDL (P = 0.04), and large VLDL (P = 0.02) concentrations than did 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 did 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 cardiovascular disease risk.

Supplementary key words inflammation • fat load • postprandial response • triglyceride-rich lipoproteins • cardiovascular disease

Abbreviations: CVD, cardiovascular disease; GOLDN, Genetics of Lipid Lowering Drugs and Diet Network; IL-6, interleukin-6; PPL, postprandial lipemia; SNP, single-nucleotide polymorphism; TG, triglyceride; TRL, TG-rich lipoprotein

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