Published online before print May 8, 2003, doi: 10.1161/01.RES.0000075600.87675.16
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2003 American Heart Association, Inc.
Clinical Research |
Biochemical and Genetic Association of Plasma Apolipoprotein A-II Levels With Familial Combined Hyperlipidemia
From the Department of Human Genetics (H.A., R.M.C., A.J.L.), Medicine (L.W.C., A.J.L.), and Microbiology and Molecular Genetics (A.J.L.), and Molecular Biology Institute (A.J.L.), University of California, Los Angeles, Calif; and the Department of Medicine and the Cardiovascular Research Institute Maastricht (CARIM) (T.W.A.d.B.), Academic Hospital, Maastricht, the Netherlands.
Correspondence to Hooman Allayee, PhD, Department of Human Genetics, Gonda Genetics Research Center, Room 6524, UCLA School of Medicine, 695 Charles Young Dr South, Los Angeles, CA 90095. E-mail hallayee{at}ucla.edu
Apolipoprotein A-II (apoA-II) is a major protein on high-density lipoprotein (HDL) particles, and in mice, its levels are associated with triglyceride and glucose metabolism. In particular, transgenic mice overexpressing apoA-II exhibit hypertriglyceridemia, increased body fat, and insulin resistance, whereas apoA-II-null mice have decreased triglycerides and increased insulin sensitivity. Given the phenotypic overlap between familial combined hyperlipidemia (FCH) and apoA-II transgenic mice, we investigated the relationship of apoA-II to this disorder. Despite having lower HDL-cholesterol (HDL-C), FCH subjects had higher apoA-II levels compared with unaffected relatives (P<0.00016). Triglyceride and HDL-C levels were significant predictors of apoA-II, demonstrating that apoA-II variation is associated with several FCH-related traits. After adjustment for multiple covariates, there was evidence for the heritability of apoA-II levels (h2=0.15; P<0.02) in this sample. A genome scan for apoA-II levels identified significant evidence (LOD=3.1) for linkage to a locus on chromosome 1q41, coincident with a suggestive linkage for triglycerides (LOD score=1.4). Thus, this locus may have pleiotropic effects on apoA-II and FCH traits. Our results demonstrate that apoA-II is biochemically and genetically associated with FCH and may serve as a useful marker for understanding the mechanism by which FCH develops.
Key Words: apolipoprotein A-II • genetics • metabolic syndrome • triglycerides • insulin resistance
This article has been cited by other articles:
 |
|
 |
|
  T. Koike, S. Kitajima, Y. Yu, Y. Li, K. Nishijima, E. Liu, H. Sun, A. B. Waqar, N. Shibata, T. Inoue, et al. Expression of Human ApoAII in Transgenic Rabbits Leads to Dyslipidemia: A New Model for Combined Hyperlipidemia Arterioscler Thromb Vasc Biol, December 1, 2009; 29(12): 2047 - 2053. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. W. Castellani, C. N. Nguyen, S. Charugundla, M. M. Weinstein, C. X. Doan, W. S. Blaner, N. Wongsiriroj, and A. J. Lusis Apolipoprotein AII Is a Regulator of Very Low Density Lipoprotein Metabolism and Insulin Resistance J. Biol. Chem., April 25, 2008; 283(17): 11633 - 11644. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Delgado-Lista, F. Perez-Jimenez, T. Tanaka, P. Perez-Martinez, Y. Jimenez-Gomez, C. Marin, J. Ruano, L. Parnell, J. M. Ordovas, and J. Lopez-Miranda An Apolipoprotein A-II Polymorphism (-265T/C, rs5082) Regulates Postprandial Response to a Saturated Fat Overload in Healthy Men J. Nutr., September 1, 2007; 137(9): 2024 - 2028. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. G. D. Silva, L. A. Schneeweis, S. C. Krishnan, X. Zhang, P. H. Axelsen, and W. S. Davidson The Structure of Apolipoprotein A-II in Discoidal High Density Lipoproteins J. Biol. Chem., March 30, 2007; 282(13): 9713 - 9721. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. G. J. Brouwers, R. M. Cantor, N. Kono, J. l. Yoon, C. J. H. van der Kallen, M. A. L. Bilderbeek-Beckers, M. M. J. van Greevenbroek, A. J. Lusis, and T. W. A. de Bruin Heritability and genetic loci of fatty liver in familial combined hyperlipidemia J. Lipid Res., December 1, 2006; 47(12): 2799 - 2807. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Dugue-Pujol, X. Rousset, D. Pastier, N. T. Quang, V. Pautre, J. Chambaz, M. Chabert, and A.-D. Kalopissis Human apolipoprotein A-II associates with triglyceride-rich lipoproteins in plasma and impairs their catabolism J. Lipid Res., December 1, 2006; 47(12): 2631 - 2639. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. W. Castellani, P. Gargalovic, M. Febbraio, S. Charugundla, M.-L. Jien, and A. J. Lusis Mechanisms mediating insulin resistance in transgenic mice overexpressing mouse apolipoprotein A-II J. Lipid Res., December 1, 2004; 45(12): 2377 - 2387. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.M. Georgieva, M.M.J. van Greevenbroek, R.M. Krauss, M.C.G.J. Brouwers, V.M.M.-J. Vermeulen, M.G. Robertus-Teunissen, C.J.H. van der Kallen, and T.W.A. de Bruin Subclasses of Low-Density Lipoprotein and Very Low-Density Lipoprotein in Familial Combined Hyperlipidemia: Relationship to Multiple Lipoprotein Phenotype Arterioscler Thromb Vasc Biol, April 1, 2004; 24(4): 744 - 749. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Bosse, Y. C. Chagnon, J-P. Despres, T. Rice, D. C. Rao, C. Bouchard, L. Perusse, and M-C. Vohl Genome-wide linkage scan reveals multiple susceptibility loci influencing lipid and lipoprotein levels in the Quebec Family Study J. Lipid Res., March 1, 2004; 45(3): 419 - 426. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Allayee, A. Ghazalpour, and A. J. Lusis Using Mice to Dissect Genetic Factors in Atherosclerosis Arterioscler Thromb Vasc Biol, September 1, 2003; 23(9): 1501 - 1509. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. E. Aouizerat and J. P. Kane Apolipoprotein A-II: Active or Passive Role in Familial Combined Hyperlipidemia Circ. Res., June 13, 2003; 92(11): 1179 - 1181. [Full Text] [PDF]
|
|