|Shen, Jian - TUFTS UNIVERSITY|
|Arnett, Donna - UNIV OF ALABAMA @ BIRM|
|Perez-Martinez, Pablo - HOSP UNIV REINA SOFIA|
|Peacock, James - UNIV OF MINNESOTA|
|Hixson, James - UNIV OF TEX HLTH SCI CEN|
|Tsai, Michael - UNIV OF MINNESOTA|
|Lai, Chao Qiang|
|Straka, Robert - UNIV OF MINNESOTA|
|Hopkins, Paul - UNIV OF UTAH|
Submitted to: Journal of Lipid Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: April 16, 2008
Publication Date: August 1, 2008
Citation: Shen, J., Arnett, D.K., Perez-Martinez, P., Parnell, L.D., Peacock, J.M., Hixson, J.E., Tsai, M.Y., Lai, C., Straka, R.J., Hopkins, P.N., Ordovas, J.M. 2008. The effect of IL6-174C/G polymorphisms on postprandial triglycerides metabolism in the GOLDN study. Journal of Lipid Research. 49:1839-1845. Interpretive Summary: Cardiovascular diseases (CVD) are the major cause of mortality among adults in the US and across the world. CVD is very multifactorial and some of the traditional risk factors include hypertension, and elevated blood lipids of cholesterol and glucose. More recently, chronic inflammation has been added to the list of factors that may predispose to increased CVD risk. The inflammation status can be examined by measuring certain products in blood such as one called C-reactive protein or another one known as interleukin-6 (IL6). Given the relation between the later and increased CVD risk we examined the genetic and dietary factors that could increase IL6 levels and thus, CVD risk. For this purpose, we investigated in a large White population. living in the US, the relation between common mutation in the gene coding for IL6 and blood IL6 levels to determine if such mutations could be used as early and reliable predictor of CVD risk. We found that one of those mutations, known as -174C/G was a predictor of blood IL6 concentrations. Moreover, people with this mutation were not able to assimilate the fat in the diet as well as those who did not have the mutation, resulting in a blood lipid profile after ingesting a meal more conductive to increased risk of cardiovascular disease. Therefore, our data reveals that the presence of this common mutation in the IL6 places those who carry such mutation at a higher risk of CVD both due to higher inflammation and worse lipid levels, especially after the ingestion of food. This knowledge could help to identify subjects with genetic predisposition to cardiovascular diseases decades before the expression of the disease and to provide more personalized and aggressive dietary advice to prevent the disease.
Technical Abstract: 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 genetic variants 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.