| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 1997;96:1737-1744.)
© 1997 American Heart Association, Inc.
Articles |
Heterozygous Lipoprotein Lipase Deficiency
Frequency in the General Population, Effect on Plasma Lipid Levels, and Risk of Ischemic Heart Disease
From the Department of Clinical Biochemistry, Herlev University Hospital, Herlev (B.G.N., S.A., H.H.W., A.T.-H.); the Copenhagen City Heart Study, Rigshospitalet, National University Hospital (B.G.N., G.J., A.T.-H.); and the Department of Medicine B, Division of Cardiology (R.S.) and Department of Clinical Biochemistry (A.T.-H.), Rigshospitalet, National University Hospital, Copenhagen, Denmark.
Background Patients with mutations on both alleles of the lipoprotein lipase gene resulting in complete lipoprotein lipase deficiency exhibit the chylomicronemia syndrome with severe hypertriglyceridemia and increased risk of pancreatitis and possibly of ischemic heart disease. This study examined frequency, lipid levels, and risk of ischemic heart disease for heterozygous carriers of lipoprotein lipase mutations known to cause the chylomicronemia syndrome in the homozygous state.
Methods and Results Two mutations were screened for in 9259
individuals in a general population sample and in 948 patients with
verified ischemic heart disease. The percent frequencies of
heterozygous individuals with the Gly188
Glu and
Ile194Thr substitutions in the general population were
0.06% (95% CI, 0.04% to 0.23%) and 0% (95% CI, 0.00% to 0.12%),
respectively. The Gly188Glu substitution was associated
with an increase in plasma triglycerides of 0.8±0.3
mmol/L (mean±SEM) and a decrease in plasma HDL
cholesterol, apo A-I, and glucose levels of 0.45±0.07
mmol/L, 17±6 mg/dL, and 1.1±0.2 mmol/L, respectively. On
multiple logistic regression analysis allowing for age, sex,
plasma cholesterol, plasma lipoprotein (a), hypertension,
diabetes mellitus, smoking, and body mass index, both plasma
triglycerides and HDL cholesterol levels were
independent predictors of ischemic heart disease. Finally, the
Gly188Glu substitution was more common among patients
with verified ischemic heart disease (percent frequency of
heterozygous individuals, 0.32%) than among individuals from the
general population (odds ratio, 4.9; 95% CI, 1.2 to 19.6). The effects
of the Gly188Glu substitution were more pronounced than
those of the common Asn291Ser substitution.
Conclusions Heterozygous lipoprotein lipase deficiency due
to the Gly188Glu substitution appears to increase plasma
triglycerides and reduce HDL levels and may thereby
predispose carriers to ischemic heart disease.
Key Words: atherosclerosis • coronary disease • lipoproteins • genes
This article has been cited by other articles:
 |
|
 |
|
  L. Shan, X.-C. Yu, Z. Liu, Y. Hu, L. T. Sturgis, M. L. Miranda, and Q. Liu The Angiopoietin-like Proteins ANGPTL3 and ANGPTL4 Inhibit Lipoprotein Lipase Activity through Distinct Mechanisms J. Biol. Chem., January 16, 2009; 284(3): 1419 - 1424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Frikke-Schmidt, B. G. Nordestgaard, M. C. A. Stene, A. A. Sethi, A. T. Remaley, P. Schnohr, P. Grande, and A. Tybjaerg-Hansen Association of Loss-of-Function Mutations in the ABCA1 Gene With High-Density Lipoprotein Cholesterol Levels and Risk of Ischemic Heart Disease JAMA, June 4, 2008; 299(21): 2524 - 2532. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A J Hooper, G M Crawford, J M Brisbane, K Robertson, G F Watts, F M van Bockxmeer, and J R Burnett Familial lipoprotein lipase deficiency caused by known (G188E) and novel (W394X) LPL gene mutations Ann Clin Biochem, January 1, 2008; 45(1): 102 - 105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Takeuchi, M. Takahashi, K. Sakano, M. Mutoh, N. Niho, M. Yamamoto, H. Sato, T. Sugimura, and K. Wakabayashi Suppression of N-nitrosobis(2-oxopropyl)amine-induced pancreatic carcinogenesis in hamsters by pioglitazone, a ligand of peroxisome proliferator-activated receptor {gamma} Carcinogenesis, August 1, 2007; 28(8): 1692 - 1696. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. H. Wittrup, R. V. Andersen, A. Tybjaerg-Hansen, G. B. Jensen, and B. G. Nordestgaard Combined Analysis of Six Lipoprotein Lipase Genetic Variants on Triglycerides, High-Density Lipoprotein, and Ischemic Heart Disease: Cross-Sectional, Prospective, and Case-Control Studies from the Copenhagen City Heart Study J. Clin. Endocrinol. Metab., April 1, 2006; 91(4): 1438 - 1445. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Pruneta-Deloche, C. Marcais, L. Perrot, A. Sassolas, M. Delay, B. Estour, M. Lagarde, and P. Moulin Combination of Circulating Antilipoprotein Lipase (Anti-LPL) Antibody and Heterozygous S172 fsX179 Mutation of LPL Gene Leading to Chronic Hyperchylomicronemia J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 3995 - 3998. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Ziouzenkova, S. Perrey, L. Asatryan, J. Hwang, K. L. MacNaul, D. E. Moller, D. J. Rader, A. Sevanian, R. Zechner, G. Hoefler, et al. Lipolysis of triglyceride-rich lipoproteins generates PPAR ligands: Evidence for an antiinflammatory role for lipoprotein lipase PNAS, March 4, 2003; 100(5): 2730 - 2735. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Merkel, R. H. Eckel, and I. J. Goldberg Lipoprotein lipase: genetics, lipid uptake, and regulation J. Lipid Res., December 1, 2002; 43(12): 1997 - 2006. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Pennacchio, M. Olivier, J. A. Hubacek, R. M. Krauss, E. M. Rubin, and J. C. Cohen Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels Hum. Mol. Genet., November 15, 2002; 11(24): 3031 - 3038. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Sethi, A. Tybjaerg-Hansen, M.-L. M. Gronholdt, R. Steffensen, P. Schnohr, and B. G. Nordestgaard Angiotensinogen Mutations and Risk for Ischemic Heart Disease, Myocardial Infarction, and Ischemic Cerebrovascular Disease: Six Case-Control Studies from the Copenhagen City Heart Study Ann Intern Med, May 15, 2001; 134(10): 941 - 954. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Sethi, B. G. Nordestgaard, B. Agerholm-Larsen, E. Frandsen, G. Jensen, and A. Tybjarg-Hansen Angiotensinogen Polymorphisms and Elevated Blood Pressure in the General Population : The Copenhagen City Heart Study Hypertension, March 1, 2001; 37(3): 875 - 881. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Agerholm-Larsen, A. Tybjarg-Hansen, P. Schnohr, R. Steffensen, and B. G. Nordestgaard Common Cholesteryl Ester Transfer Protein Mutations, Decreased HDL Cholesterol, and Possible Decreased Risk of Ischemic Heart Disease : The Copenhagen City Heart Study Circulation, October 31, 2000; 102(18): 2197 - 2203. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Agerholm-Larsen, B. G. Nordestgaard, R. Steffensen, G. Jensen, and A. Tybjarg-Hansen Elevated HDL Cholesterol Is a Risk Factor for Ischemic Heart Disease in White Women When Caused by a Common Mutation in the Cholesteryl Ester Transfer Protein Gene Circulation, April 25, 2000; 101(16): 1907 - 1912. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Clee, N. Bissada, F. Miao, L. Miao, A. D. Marais, H. E. Henderson, P. Steures, J. McManus, B. McManus, R. C. LeBoeuf, et al. Plasma and vessel wall lipoprotein lipase have different roles in atherosclerosis J. Lipid Res., April 1, 2000; 41(4): 521 - 531. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. Frikke-Schmidt, A. Tybjaerg-Hansen, R. Steffensen, G. Jensen, and B.o. G. Nordestgaard Apolipoprotein E genotype: epsilon32 women are protected while epsilon43 and epsilon44 men are susceptible to ischemic heart disease: The Copenhagen City Heart Study J. Am. Coll. Cardiol., April 1, 2000; 35(5): 1192 - 1199. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Marshall, K. Tordjman, H. H. Host, N. J. Ensor, G. Kwon, C. A. Marshall, T. Coleman, M. L. McDaniel, and C. F. Semenkovich Relative Hypoglycemia and Hyperinsulinemia in Mice with Heterozygous Lipoprotein Lipase (LPL) Deficiency. ISLET LPL REGULATES INSULIN SECRETION J. Biol. Chem., September 24, 1999; 274(39): 27426 - 27432. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Yagyu, S. Ishibashi, Z. Chen, J.-i. Osuga, M. Okazaki, S. Perrey, T. Kitamine, M. Shimada, K. Ohashi, K. Harada, et al. Overexpressed lipoprotein lipase protects against atherosclerosis in apolipoprotein E knockout mice J. Lipid Res., September 1, 1999; 40(9): 1677 - 1685. [Abstract] [Full Text]
|
|
|
|
|
|
H. H. Wittrup, A. Tybjærg-Hansen, and B. G. Nordestgaard Lipoprotein Lipase Mutations, Plasma Lipids and Lipoproteins, and Risk of Ischemic Heart Disease : A Meta-Analysis Circulation, June 8, 1999; 99(22): 2901 - 2907. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. H. Wittrup, A. Tybjærg-Hansen, R. Steffensen, S. S. Deeb, J. D. Brunzell, G. Jensen, and B. G. Nordestgaard Mutations in the lipoprotein lipase Gene Associated With Ischemic Heart Disease in Men : The Copenhagen City Heart Study Arterioscler. Thromb. Vasc. Biol., June 1, 1999; 19(6): 1535 - 1540. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. E. Henderson, J. J. P. Kastelein, A. H. Zwinderman, E. Gagné, J. W. Jukema, P. W. A. Reymer, B. E. Groenemeyer, K. I. Lie, A. V. G. Bruschke, M. R. Hayden, et al. Lipoprotein lipase activity is decreased in a large cohort of patients with coronary artery disease and is associated with changes in lipids and lipoproteins J. Lipid Res., April 1, 1999; 40(4): 735 - 743. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. Tybjarg-Hansen, R. Steffensen, H. Meinertz, P. Schnohr, and B. G. Nordestgaard Association of Mutations in the Apolipoprotein B Gene with Hypercholesterolemia and the Risk of Ischemic Heart Disease N. Engl. J. Med., May 28, 1998; 338(22): 1577 - 1584. [Abstract] [Full Text] [PDF]
|
|