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United States Department of Agriculture

Agricultural Research Service

Title: Interleukin 1B genetic polymorphisms interact with polyunsaturated fatty acids to affect risk of the metabolic syndrome in the GOLDN Study

Authors
item Shen, Jian - TUFTS UNIVERSITY
item Arnett, Donna - UNIV. OF ALABAMA-BIRMINGH
item Peacock, James - UNIV. OF MINNESOTA
item Parnell, Laurence
item Aldi, Kraja - WASHINGTON UNIVERSITY
item Hixson, James - UNIV. OF TEXAS
item Tsai, Michael - UNIV. OF MINNESOTA
item Kabagambe, Edmond - UNIV. OF ALABAMA-BIRMING
item Lai, Chao Qiang
item Stratka, Robert - UNIV. OF MINNESOTA
item Ordovas, Jose

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 21, 2007
Publication Date: August 1, 2007
Citation: Shen, J., Arnett, D.K., Peacock, J.M., Parnell, L.D., Aldi, K., Hixson, J.E., Tsai, M.Y., Kabagambe, E.K., Lai, C., Stratka, R.J., Ordovas, J.M. 2007. Interleukin 1B genetic polymorphisms interact with polyunsaturated fatty acids to affect risk of the metabolic syndrome in the GOLDN Study. Journal of Nutrition. 137(8):1846-1851.

Interpretive Summary: Metabolic syndrome (MetS) is the cluster of risk factors for cardiovascular diseases (CVD), including abdominal obesity, hypertension, high triglyceride, low HDL cholesterol and high fasting glucose. MetS substantially increases the risk of CVD and type II diabetes and therefore has become one of the major public health threats in the United States. The etiology of MetS involves multiple genetic and environmental factors, with diet being the major environmental factor. In this paper, researchers found that genetic mutations at the IL1B gene which encodes protein playing an important role in inflammatory pathway significantly affected individual risk to MetS. Furthermore, researchers demonstrated that the genetic impact is influenced by dietary fat, using fatty acids composition of the erythrocyte membrane as a biomarker of dietary intake. The deleterious effects of the IL1B gene mutation only occurs among subjects with low polyunsaturated fatty acid intake, suggesting potential unhealthy dietary habit. The results provide insight into causal role of chronic inflammation in the development of MetS. The knowledge gained from this research underscores the importance of gene and environmental interaction in MetS process.

Technical Abstract: Chronic inflammation has been identified as an important component of the metabolic syndrome (MetS). Therefore, environmental and genetic factors contributing to the variation of inflammatory responses could affect individuals’ susceptibility to the MetS. We investigated the association between common IL1' genetic polymorphisms, inflammation and the MetS, and its modulation by diet-related variables (i.e., erythrocyte membrane fatty acid composition) in a White US population. IL1' SNPs (-1473G>C, -511G>A, -31T>C, 3966C>T, 6054G>A), clinical and biochemical measurements were characterized in a total of 1120 subjects (540 males and 580 females) participating in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study. The 6054 G>A SNP was significantly associated with plasma C-reactive protein (P=0.054), adiponectin (P=0.021) and the prevalence of MetS (P=0.004). Moreover, there was a significant interaction between the 6054G>A SNP and erythrocyte membrane (n-3) PUFA (P=0.019). Among subjects with low (n-3) PUFA content (below the median), the 6054 G allele was significantly associated with increased risk of the MetS (OR: 3.29, 95%CI: 1.49-7.26 for GG and OR: 1.95, 95%CI: 0.85-4.46 for GA, P<0.001) compared to the AA genotype, but there was no significant genotype associations among subjects with high (n-3) PUFA content (above the median). Further analyses supported a significant haplotype global effect on the MetS (P=0.017) among subjects with low (n-3) PUFA content. These results suggest that IL1' genetic variants are associated with measures of chronic inflammation and the MetS risk, and the genetic influences are more evident among subjects with low (n-3) PUFA intake.

Last Modified: 8/1/2014
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