Lipoprotein lipase S447X: a naturally occurring gain-of-function mutation.
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 LPL(S447X) 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 LPL(S447X). This review summarizes the current literature on this interesting LPL variant.
Department of Vascular Medicine, Academic Medical Centre, University of Amsterdam, The Netherlands.
Jaap
J
Rip
Melchior C
MC
Nierman
Colin J
CJ
Ross
Jan Wouter
JW
Jukema
Michael R
MR
Hayden
John J P
JJ
Kastelein
Erik S G
ES
Stroes
Jan Albert
JA
Kuivenhoven
D000818:Animals; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics*; D009154:Mutation / Q000502:physiology*; D012694:Serine
D012694:Serine; D008071:Lipoprotein Lipase