(Circulation. 1996;94:1913-1918.)
© 1996 American Heart Association, Inc.
Articles |
The Asp9 Asn Mutation in the Lipoprotein Lipase Gene Is Associated With Increased Progression of Coronary Atherosclerosis
the Department of Cardiology, University Hospital, Leiden (J.W.J., J.H.C.R., A.V.G.B.); the Department of Cardiology, University Hospital, Groningen (A.J.v.B.); the Department of Vascular Medicine, Academical Medical Center, Amsterdam (B.G., T.B., J.J.P.K.); the Department of Medical Statistics, Leiden University, Leiden (A.H.Z.); the Department of Cardiology, Medisch Centrum, Alkmaar (J.A.H.); the Department of Cardiology, Medisch Spectrum Twente, Enschede (G.P.M.); and the Department of Biochemistry, Erasmus University, Rotterdam (H.J.); The Netherlands; and the Department of Medical Genetics, University of British Columbia, Vancouver, Canada (E.G., M.R.H.).
Correspondence to J.W. Jukema, MD, Department of Cardiology, University Hospital Leiden, Bldg 1, C5-P, Rijnsburgerweg 10, 2333 AA Leiden, The Netherlands.
Background Many patients suffering from premature coronary artery disease report a family history for such events. A mutation in a particular gene, which confers susceptibility for atherosclerosis, will be found more frequently in individuals suffering from coronary atherosclerosis than in the general population. We have recently reported the identification of an Asp9 Asn substitution in the lipoprotein lipase (LPL) enzyme. We analyzed the impact of this mutation on the progression of coronary atherosclerosis and the effect of pravastatin in both carriers and noncarriers.
Methods and Results All patients were enrolled in the quantitative coronary angiographic clinical trial REGRESS, which studied the impact of pravastatin therapy on coronary atherosclerosis. The Asp9 Asn mutation was identified in 38 of 819 (4.8%) patients. Carriers of the mutation more often had a positive family history of cardiovascular disease and lower HDL cholesterol levels than noncarriers. In the placebo group, carriers showed more progression of coronary atherosclerosis than noncarriers: mean reduction of the minimum obstruction diameter of -0.25 mm versus -0.12 mm (P=.029) and increase of percentage diameter stenosis of 6.4% versus 1.4% (P=.004). Moreover, the adjusted relative risk for a clinical event for carriers was calculated at 2.16 (95% CI, 1.09 to 4.29; P=.027). Although the lipid-lowering effect of pravastatin was attenuated in carriers, it appeared that these patients showed a response similar to noncarriers in terms of less progression of atherosclerosis and event-free survival.
Conclusions This study shows that heterozygosity for a mutation in the LPL gene, which causes only subtle changes in fasting plasma lipids, may promote the progression of coronary atherosclerosis and diminish clinical event–free survival.
Key Words: lipoproteins • atherosclerosis • genes
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