%0 Journal Article
%T ANGPTL4 variants E40K and T266M are associated with lower fasting triglyceride levels in Non-Hispanic White Americans from the Look AHEAD Clinical Trial
%A Melissa C Smart-Halajko
%A Alyson Kelley-Hedgepeth
%A Maria Montefusco
%A Jackie A Cooper
%A Alan Kopin
%A Jeanne M McCaffery
%A Ashok Balasubramanyam
%A Henry J Pownall
%A David M Nathan
%A Inga Peter
%A Philippa J Talmud
%A Gordon S Huggins
%A the Look AHEAD Study
%J BMC Medical Genetics
%D 2011
%I BioMed Central
%R 10.1186/1471-2350-12-89
%X 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.Among non-Hispanic White Look AHEAD participants, ANGPTL4 K40 carriers had mean triglyceride levels of 1.61 ¡À 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 ¡À 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.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.Studies in large Western [1] and Asian [2] population cohorts have demonstrated an independent association between elevated triglyceride levels and cardiovascular disease (CVD) risk. Triglyceride levels may become elevated through independent effects caused by the metabolic syndrome and type 2 diabetes (T2D), both well-established risk factors for CVD [3]. Furthermore, lifestyle changes can significantly reduce triglyceride levels [4] and may moderate the risk of CVD [5].Lipoprotein lipase (LPL) regulates triglyceride levels by hydrolyzing the triglyceride component of circulating lipoproteins [6,7]. At least some of the effects of T2D on triglycerides are mediated by LPL, whose expression and activity is influenced by insulin [6,7]. The angiopoietin-like protein 4 (Angptl4) peptide, which is primarily expressed in the
%U http://www.biomedcentral.com/1471-2350/12/89