title: Differential association of plasma angiopoietin-like proteins 3 and 4 with lipid and metabolic traits.
abstract: OBJECTIVE
  Angiopoietin-like protein 3 (ANGPTL3) and 4 (ANGPTL4) are secreted proteins that inhibit lipoprotein lipase in vitro. Genetic variants at the ANGPTL3 and ANGPTL4 gene loci are significantly associated with plasma lipid traits. The aim of this study was to evaluate the association of plasma ANGPTL3 and ANGPTL4 concentrations with lipid and metabolic traits in a large community-based sample.
  
  
  RESULTS
  Plasma ANGPTL3 and ANGPTL4 levels were measured in 1770 subjects using a validated ELISA assay. A Pearson unadjusted correlation analysis and a linear regression analysis adjusting for age, sex, and race were performed. ANGPTL3 levels were significantly positively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels (both P<2×10(-5)) but not triglycerides. In contrast, ANGPTL4 levels were significantly negatively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol (both P<2×10(-5)) and positively associated with triglycerides (P=0.003). In addition, ANGPTL4, but not ANGPTL3, levels were significantly positively associated with fasting blood glucose and metabolic syndrome.
  
  
  CONCLUSIONS
  Despite having similar biochemical effects in vitro, plasma ANGPTL3 and ANGPTL4 concentrations have nearly opposite relationships with plasma lipids. ANGPTL4 is strongly negatively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol and positively with multiple features of the metabolic syndrome including triglycerides, whereas ANGPTL3 is positively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol and not with metabolic syndrome traits including triglycerides. Although ANGPTL3 and ANGPTL4 both inhibit lipoprotein lipase in vitro and influence lipoprotein metabolism in vivo, the physiology of these related proteins and their effects on lipoproteins is clearly divergent and complex.
authors.affiliation: From the Department of Medicine and Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (N.M., A.Q., L.Q., M.P.R., D.J.R.); Department of Medicine, University of California at San Francisco (A.N.Q.); and National Heart, Lung, and Blood Institute, Bethesda, MD (N.N.M.).
authors.forename: Nidhi
authors.initials: N
authors.lastname: Mehta
authors.forename: Arman
authors.initials: A
authors.lastname: Qamar
authors.forename: Liming
authors.initials: L
authors.lastname: Qu
authors.forename: Atif N
authors.initials: AN
authors.lastname: Qasim
authors.forename: Nehal N
authors.initials: NN
authors.lastname: Mehta
authors.forename: Muredach P
authors.initials: MP
authors.lastname: Reilly
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Rader
mesh_terms: D000091303:Angiopoietin-Like Protein 3; D000075803:Angiopoietin-Like Protein 4; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006801:Humans; D016014:Linear Models; D050356:Lipid Metabolism / Q000235:genetics; D016015:Logistic Models; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D010641:Phenotype; D014280:Triglycerides / Q000097:blood
chemical_list: C479896:ANGPTL3 protein, human; C474772:ANGPTL4 protein, human; D000091303:Angiopoietin-Like Protein 3; D000075803:Angiopoietin-Like Protein 4; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D015415:Biomarkers; D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides
keywords: angiopoietins; cholesterol, HDL; cholesterol, LDL; diabetes mellitus; epidemiology; lipid metabolism; lipids; lipoproteins; triglycerides