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(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

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