Interleukin 1B variant -1473G/C (rs1143623) influences triglyceride and interleukin 6 metabolism

Authors: DELGADO-LISTA, JAVIER - University Of Reina Sofia; GARCIA-RIOS, ANTONIO - University Of Reina Sofia; PEREZ-MARTINEZ, PABLO - University Of Reina Sofia; SOLIVERA, JUAN - University Of Reina Sofia; YUBERO-SERRANO, ELENA - University Of Reina Sofia; FUENTES, FRANCISCO - University Of Reina Sofia; Parnell, Laurence; SHEN, JIAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; GOMEZ, PURIFICACION - University Of Reina Sofia; JIMENEZ-GOMEZ, YOLANDA - University Of Reina Sofia; GOMEZ-LUNA, MARIA - University Of Reina Sofia; MARIN, CARMEN - University Of Reina Sofia; BELISLE, SARAH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; RODRIGUEZ-CANTALEJO, F - University Of Reina Sofia; MEYDANI, SIMIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; PEREZ-JIMENEZ, FRANCISCO - University Of Reina Sofia; LOPEZ-MIRANDA, JOSE - University Of Reina Sofia

Submitted to: Journal of Clinical Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/19/2011
Publication Date: 5/1/2011
Citation: Delgado-Lista, J., Garcia-Rios, A., Perez-Martinez, P., Solivera, J., Yubero-Serrano, E.M., Fuentes, F., Parnell, L.D., Shen, J., Gomez, P., Jimenez-Gomez, Y., Gomez-Luna, M.J., Marin, C., Belisle, S.E., Rodriguez-Cantalejo, F., Meydani, S.N., Ordovas, J.M., Perez-Jimenez, F., Lopez-Miranda, J. 2011. Interleukin 1B variant -1473G/C (rs1143623) influences triglyceride and interleukin 6 metabolism. Journal of Clinical Endocrinology and Metabolism. 96(5):E816-820.

Interpretive Summary: A key modulator of the immune response in humans is interleukin 1b (IL1B), which exerts its functions in a signal cascade via interleukin 6 (IL6). Importantly, fatty meals cause a temporary rise in triglyceride levels in the blood, which promotes widespread but low-grade inflammation, but the degree to which this actually takes place is highly variable from person to person. Some of that variability is due to genetic differences between persons within the IL1B and IL6 genes. We sought to define the impact of one such point of genetic variation – that within the region controlling activity of IL1B. Eighty-eight healthy young men were assessed for the version of the genetic variant in this IL1B control zone and were fed a test meal rich in saturated fat. Blood samples were examined for levels of cholesterol and triglycerides during an 11-hour course after the feeding. A parallel study was conducted in 477 people who were older than 65 years. Taken together, the results of these studies show that people who carry the less common form of the genetic variant in the IL1B control zone have higher after-meal responses to both the levels of cholesterol and triglycerides and inflammation-promoting compounds. Thus, these individuals would be at higher risk of developing cardiovascular disease on two fronts: the blood levels of cholesterol and triglycerides remain extra high after a high-fat meal and the inflammation response to such a meal, which can lead to tissue damage in arteries, is elevated beyond the norm.

Technical Abstract: Interleukin 1b (IL1B or IL-1ß), is a key modulator of the immune response which exerts its functions mainly via interleukin 6 (IL6) regulation. Fatty meals cause transient hypertriglyceridemia and are considered to be proinflammatory, but the extent of these responses shows high interindividual susceptibility. We evaluated the influence of a genetic variant located in the promoter region of IL1B (-1473G/C) on postprandial lipids and IL6. Methods and Results: Eighty-eight healthy young men were genotyped for IL1B -1473G/C (rs1143623) and were fed a saturated fatty acid-rich meal. Serial blood samples were drawn for 11 hours after the meal, and lipid fractions and IL6 were assayed. A parallel study examined fasting lipids in 477 people aged >65 years old. Healthy young men carriers of the minor C allele showed higher postprandial triglycerides (TG), and those carried into large triglyceride rich lipoproteins (TRL). In addition, they showed higher postprandial IL6 concentration. In aged persons, CC homozygotes showed higher TG and cholesterol (CHOL) fasting levels. Conclusions: Our work shows that healthy young men carriers of the minor allele for IL1B -1473G/C display higher postprandial lipemia and inflammatory responses. In elderly subjects, homozygotes for the minor allele have higher fasting TG and CHOL levels.