on March 30, 2006
Published online before print March 30, 2006, doi: 10.1161/01.ATV.0000219283.10832.43
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Submitted on January 20, 2006
Accepted on March 9, 2006
Lipoprotein Lipase S447X. A Naturally Occurring Gain-of-Function Mutation
Jaap Rip ;
From the Department of Vascular Medicine (J.R., M.C.N., J.J.P.K., E.S.G.S., J.A.K.), Academic Medical Center, University of Amsterdam, the Netherlands; Leiden University Medical Center (J.W.J.), Department of Cardiology, Leiden, The Netherlands; and the Center for Molecular Medicine and Therapeutics (C.J.R., M.R.H.), University of British Columbia, Vancouver, British Columbia, Canada
* To whom correspondence should be addressed. E-mail: j.a.kuivenhoven{at}amc.uva.nl.
Abstract--Lipoprotein lipase (LPL) hydrolyzes triglycerides in the circulation and promotes the hepatic uptake of remnant lipoproteins. Since the gene was cloned in 1989, more than 100 LPL gene mutations have been identified, the majority of which cause loss of enzymatic function. In contrast to this, the naturally occurring LPLS447X variant is associated with increased lipolytic function and an anti-atherogenic lipid profile and can therefore be regarded as a gain-of-function mutation. This notion combined with the facts that 20% of the general population carries this prematurely truncated LPL and that it may protect against cardiovascular disease has led to extensive clinical and basic research into this frequent LPL mutant. It is only until recently that we begin to understand the molecular mechanisms that underlie the beneficial effects associated with LPLS447X. This review summarizes the current literature on this interesting LPL variant.
Key words: cardiovascular disease • lipids • lipoprotein lipase • lipoproteins • S447X
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