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, José M. Ordovás

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1839-1845
Number of pages7
JournalJournal of lipid research
Volume49
Issue number8
DOIs
StatePublished - Aug 2008

Keywords

  • Cardiovascular disease
  • Fat load
  • Inflammation
  • Postprandial response
  • Triglyceride-rich lipoproteins

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