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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1181.)
© 2002 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Characterization of LDL Particle Size Among Carriers of a Defective or a Null Mutation in the Lipoprotein Lipase Gene

The Québec LIPD Study

Isabelle L. Ruel; Daniel Gaudet; Patrice Perron; Jean Bergeron; Pierre Julien; Benoît Lamarche

From the Institute on Nutraceuticals and Functional Foods (I.L.R., B.L.), the Lipid Research Center (I.L.R., J.B., P.J., B.L.), CHUL Research Center, and the University of Montréal Community Genomic Medicine Center (D.G., P.P.), Chicoutimi Hospital, Québec, Canada.

Correspondence to Benoît Lamarche, PhD, Institute on Nutraceuticals and Functional Foods, Paul-Comtois Pavillon, Laval University, Québec, G1K 7P4, Canada. E-mail benoit.lamarche@ inaf.ulaval.ca

Objective— The objective of the present study was to compare the impact of the null P207L and defective D9N mutations in the LPL gene on LDL particle size among heterozygous carriers.

Methods and Results— LDL particle size was measured on whole plasma by 2% to 16% non-denaturing polyacrylamide gradient gel electrophoresis in a cohort of 206 heterozygous carriers of either the P207L or the D9N mutation. The P207L carriers (N=88) presented with a more atherogenic lipoprotein-lipid profile compared with the D9N carriers (N=118). Accordingly, LDL particle size was smaller in the P207L carriers than in the D9N subjects (248.8± 1.0 vs 254.5±1.0 Å, P< 0.001), and the difference remained significant after adjustment for plasma triglyceride (TG) levels. The difference in LDL diameter between the P207L and the D9N carriers was 3-fold greater in individuals with plasma TG levels >3.5 mmol/L than in subjects with TG 3.5 mmol/L. The factors that statistically contributed to LDL particle size variation in multivariate analyses were plasma TG levels (11.6%) and age (6.4%) in subjects with TG levels 3.5 mmol/L and HDL cholesterol levels (15.5%) and the LPL gene mutation (null versus defective, 7.0%) in patients with TG levels >3.5 mmol/L.

Conclusions— These results suggest that the null P207L mutation in the LPL gene has a greater impact on LDL particle size than the defective D9N mutation and that this mutation-specific effect is amplified at greater plasma TG concentrations.

Key Words: lipoprotein lipase • gene • defects • LDL particle size • lipoproteins

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