TY - JOUR
T1 - ANGPTL4 variants E40K and T266M are associated with lower fasting triglyceride levels in Non-Hispanic White Americans from the Look AHEAD Clinical Trial
AU - Smart-Halajko, Melissa C.
AU - Kelley-Hedgepeth, Alyson
AU - Montefusco, Maria C.
AU - Cooper, Jackie A.
AU - Kopin, Alan
AU - McCaffrey, Jeanne M.
AU - Balasubramanyam, Ashok
AU - Pownall, Henry J.
AU - Nathan, David M.
AU - Peter, Inga
AU - Talmud, Philippa J.
AU - Huggins, Gordon S.
N1 - Funding Information:
We gratefully acknowledge the contributions of the Look AHEAD Study Group members [4]. This study is supported by the National Institutes of Health (R01 DK072497), the British Heart Foundation (PG2005/014) and additional sources listed below. This manuscript is based on a subset of the baseline data set from participants enrolled from the Look AHEAD sites at Pennington Biomedical Research Center; Massachusetts General Hospital; University of Colorado Health Sciences Center; Baylor College of Medicine; The University of Tennessee Health Science Center, University of Tennessee; University of Minnesota; St. Luke’s Roosevelt Hospital Center; University of Pennsylvania; University of Pittsburgh; and Brown University. Additional support was received from the Massachusetts General Hospital Mallinckrodt General Clinical Research Center (M01-RR-01066); the University of Colorado Health Sciences Center General Clinical Research Center (M01 RR00051) and Clinical Nutrition Research Unit (P30 DK48520); the University of Tennessee at Memphis General Clinical Research Center (M01RR00211-40); the University of Pittsburgh General Clinical Research Center (M01 RR000056 44) and NIH grant (DK 046204). Author AKH was supported by the Training Program in Cardiovascular Research (NIH, 5T32HL069770) and MCS is supported by a Unilever/BBSRC Case studentship.
PY - 2011/6/29
Y1 - 2011/6/29
N2 - 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.
AB - 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.
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U2 - 10.1186/1471-2350-12-89
DO - 10.1186/1471-2350-12-89
M3 - Article
C2 - 21714923
AN - SCOPUS:79959674534
SN - 1471-2350
VL - 12
JO - BMC Medical Genetics
JF - BMC Medical Genetics
M1 - 89
ER -