This Article Full Text Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kuivenhoven, J. A. Articles by Kastelein, J. J. P. Search for Related Content PubMed PubMed Citation Articles by Kuivenhoven, J. A. Articles by Kastelein, J. J. P. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Genetics Home Reference Hazardous Substances DB L-SERINE

(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:595-599.)
© 1997 American Heart Association, Inc.

Articles

Ser_447stop Mutation in Lipoprotein Lipase Is Associated With Elevated HDL Cholesterol Levels in Normolipidemic Males

Jan Albert Kuivenhoven; Björn E. Groenemeyer; Jolanda M. A. Boer; Paul W. A. Reymer; Riteke Berghuis; Taco Bruin; Hans Jansen; Jacob C. Seidell; ; John J. P. Kastelein

From the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Netherlands (J.A.K, B.E.G., P.W.A.R., R.B., T.B., J.J.P.K.); the Department of Chronic Diseases and Environmental Epidemiology (J.M.A.B., J.C.S.), National Institute of Public Health and Environmental Protection, Bilthoven, Netherlands; and the Departments of Internal Medicine III and Biochemistry (H.J.), Erasmus University Rotterdam, Netherlands.

Correspondence to J.A. Kuivenhoven, Academic Medical Center, Department of Vascular Medicine (G1-114), Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. E-mail: kuif{at}wnet.bos.nl.

Abstract This report describes the association between a frequent mutation in the lipoprotein lipase (LPL) gene and HDL cholesterol levels. It concerns a previously described defect that predicts a premature truncation of the LPL protein (447stop). We determined the frequency of this mutation in three groups of healthy men with low-, middle-, and upper-decile HDL cholesterol. The number of carriers of the 447stop allele was significantly greater in the high HDL group than in either the groups with normal HDL (P=.017) or low HDL (P<.0001). Additional functional assessment of this mutation did not reveal distinct differences between wild-type LPL and the LPL_447stop protein. In conclusion, we have shown that the 447stop mutation is associated with increased HDL cholesterol in healthy Dutch males, although the underlying mechanism remains to be elucidated. Because HDL cholesterol is strongly inversely related with CAD, this genotype might be of potential benefit to its carriers.

Key Words: high-density lipoprotein • lipoprotein lipase • polymorphism • restriction fragment–length polymorphism • coronary artery disease

This article has been cited by other articles:

				J. Rip, M. C. Nierman, C. J. Ross, J. W. Jukema, M. R. Hayden, J. J.P. Kastelein, E. S.G. Stroes, and J. A. Kuivenhoven Lipoprotein Lipase S447X: A Naturally Occurring Gain-of-Function Mutation Arterioscler. Thromb. Vasc. Biol., June 1, 2006; 26(6): 1236 - 1245. [Abstract] [Full Text] [PDF]

				R. A. Hegele, C. J.D. Ross, J. Twisk, J. A. Kuivenhoven, J. Rip, J. J. Kastelein, and M. R. Hayden Gene therapy with lipoprotein lipase variant S447X. Arterioscler. Thromb. Vasc. Biol., March 1, 2006; 26(3): e25 - e25. [Full Text] [PDF]

				M. C. Nierman, B. H.C.M.T. Prinsen, J. Rip, R. J. Veldman, J. A. Kuivenhoven, J. J.P. Kastelein, M. G.M. de Sain-van der Velden, and E. S.G. Stroes Enhanced Conversion of Triglyceride-Rich Lipoproteins and Increased Low-Density Lipoprotein Removal in LPLS447X Carriers Arterioscler. Thromb. Vasc. Biol., November 1, 2005; 25(11): 2410 - 2415. [Abstract] [Full Text] [PDF]

				D. J. Rader Gain-of-Function Mutations and Therapeutic Implications: Lipoprotein Lipase S447X to the Rescue Arterioscler. Thromb. Vasc. Biol., October 1, 2005; 25(10): 2018 - 2019. [Full Text] [PDF]

				C. J.D. Ross, G. Liu, J. A. Kuivenhoven, J. Twisk, J. Rip, W. van Dop, K. J.D. Ashbourne Excoffon, S. M.E. Lewis, J. J. Kastelein, and M. R. Hayden Complete Rescue of Lipoprotein Lipase-Deficient Mice by Somatic Gene Transfer of the Naturally Occurring LPLS447X Beneficial Mutation Arterioscler. Thromb. Vasc. Biol., October 1, 2005; 25(10): 2143 - 2150. [Abstract] [Full Text] [PDF]

				P. S. Monraats, J. S. Rana, M. C. Nierman, N. M.M. Pires, A. H. Zwinderman, J. J.P. Kastelein, J. A. Kuivenhoven, M. P.M. de Maat, S. Z.H. Rittersma, A. Schepers, et al. Lipoprotein Lipase Gene Polymorphisms and the Risk of Target Vessel Revascularization After Percutaneous Coronary Intervention J. Am. Coll. Cardiol., September 20, 2005; 46(6): 1093 - 1100. [Abstract] [Full Text] [PDF]

				J. Lopez-Miranda, G. Cruz, P. Gomez, C. MarIn, E. Paz, P. Perez-MartInez, F. J. Fuentes, J. M. Ordovas, and F. Perez-Jimenez The Influence of Lipoprotein Lipase Gene Variation on Postprandial Lipoprotein Metabolism J. Clin. Endocrinol. Metab., September 1, 2004; 89(9): 4721 - 4728. [Abstract] [Full Text] [PDF]

				D. Corella, M. Guillen, C. Saiz, O. Portoles, A. Sabater, J. Folch, and J. M. Ordovas Associations of LPL and APOC3 gene polymorphisms on plasma lipids in a Mediterranean population: interaction with tobacco smoking and the APOE locus J. Lipid Res., March 1, 2002; 43(3): 416 - 427. [Abstract] [Full Text] [PDF]

				S. H. McGladdery and J. J. Frohlich Lipoprotein lipase and apoE polymorphisms: relationship to hypertriglyceridemia during pregnancy J. Lipid Res., November 1, 2001; 42(11): 1905 - 1912. [Abstract] [Full Text] [PDF]

				E. J. G. Sijbrands, M. J. V. Hoffer, A. E. Meinders, L. M. Havekes, R. R. Frants, A. H. M. Smelt, and P. De Knijff Severe Hyperlipidemia in Apolipoprotein E2 Homozygotes Due to a Combined Effect of Hyperinsulinemia and an SstI Polymorphism Arterioscler. Thromb. Vasc. Biol., November 1, 1999; 19(11): 2722 - 2729. [Abstract] [Full Text] [PDF]

				S. Cheng, M. A. Grow, C. Pallaud, W. Klitz, H. A. Erlich, S. Visvikis, J. J. Chen, C. R. Pullinger, M. J. Malloy, G. Siest, et al. A Multilocus Genotyping Assay for Candidate Markers of Cardiovascular Disease Risk Genome Res., October 1, 1999; 9(10): 936 - 949. [Abstract] [Full Text]

				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]

				S. E. Humphries, V. Nicaud, J. Margalef, L. Tiret, P. J. Talmud, and f. t. EARS Lipoprotein Lipase Gene Variation Is Associated With a Paternal History of Premature Coronary Artery Disease and Fasting and Postprandial Plasma Triglycerides : The European Atherosclerosis Research Study (EARS) Arterioscler. Thromb. Vasc. Biol., April 1, 1998; 18(4): 526 - 534. [Abstract] [Full Text] [PDF]