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ANGPTL4 variants E40K and T266M are associated with lower fasting triglyceride levels in Non-Hispanic White Americans from the Look AHEAD Clinical Trial

Year: 2011
Type: article
Abstract: BACKGROUND: Elevated triglyceride levels are a risk factor for cardiovascular disease. Angiopoietin-like protein 4 (Angptl4) is a metabolic factor that raises plasma triglyceride levels by inhibiting lipoprotein lipase (LPL). In non-diabetic individuals, the ANGPTL4 coding variant E40K has been associated with lower plasma triglyceride levels while the T266M variant has been associated with more modest effects on triglyceride metabolism. The objective of this study was to determine whether ANGPTL4 E40K and T266M are associated with triglyceride levels in the setting of obesity and T2D, and whether modification of triglyceride levels by these genetic variants is altered by a lifestyle intervention designed to treat T2D. METHODS: The association of ANGPTL4 E40K and T266M with fasting triglyceride levels was investigated in 2,601 participants from the Look AHEAD Clinical Trial, all of whom had T2D and were at least overweight. Further, we tested for an interaction between genotype and treatment effects on triglyceride levels. RESULTS: Among non-Hispanic White Look AHEAD participants, ANGPTL4 K40 carriers had mean triglyceride levels of 1.61 ± 0.62 mmol/L, 0.33 mmol/L lower than E40 homozygotes (p = 0.001). Individuals homozygous for the minor M266 allele (MAF 30%) had triglyceride levels of 1.75 ± 0.58 mmol/L, 0.24 mmol/L lower than T266 homozygotes (p = 0.002). The association of the M266 with triglycerides remained significant even after removing K40 carriers from the analysis (p = 0.002). There was no interaction between the weight loss intervention and genotype on triglyceride levels. CONCLUSIONS: This is the first study to demonstrate that the ANGPTL4 E40K and T266M variants are associated with lower triglyceride levels in the setting of T2D. In addition, our findings demonstrate that ANGPTL4 genotype status does not alter triglyceride response to a lifestyle intervention in the Look AHEAD study.
DOI: 10.1186/1471-2350-12-89
Authors: the Look AHEAD Study, Melissa C Smart-Halajko, Alyson Kelley-Hedgepeth, Maria Claudia Montefusco, Jackie A Cooper, Alan Kopin, Jeanne M McCaffery, Ashok Balasubramanyam, Henry J Pownall, David M Nathan, Inga Peter, Philippa J Talmud, Gordon S Huggins
Institutions: University College London, Tufts Medical Center, The Royal Free Hospital, British Heart Foundation, Brown University, Baylor College of Medicine, Miriam Hospital, Massachusetts General Hospital, Harvard University, Icahn School of Medicine at Mount Sinai
Language: English
Field: Medicine
Open Access status: gold
Estimated APC paid: $2,380
Funders: Massachusetts General Hospital, Brown University, University of Pennsylvania, Tufts Medical Center, University of Minnesota, University of Pittsburgh, British Heart Foundation, National Institutes of Health, Health Science Center, University of Tennessee, Biotechnology and Biological Sciences Research Council, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources
Awards: G1187123934, G2037811546, G220748524, G3317573464, General Clinical Research Center, G3698430938, G4818134524, G4929737355, GENERAL CLINICAL RESEARCH CENTER, G66933475, G6756527295, G753776066, G803155717, Obesity/Nutrition Research Center, G8755979682, G881343144, G9000013878, G9000030515, G9000085504, G9000113229, G9000141685, G9000335983, Diabetes Research Center, G980169708
OpenAlex ID: W2018331957
FWCI: 2.456
Cites: 20
Cited by: 37
Related to: 10