Characterization of LDL particle size among carriers of a defective or a null mutation in the lipoprotein lipase gene: the Québec LIPD Study.
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.


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 A, 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 < or =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 < or =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.
Ruel
Isabelle L
IL
Institute on Nutraceuticals and Functional Foods, CHUL Research Center, Québec, Canada.
Gaudet
Daniel
D
Perron
Patrice
P
Bergeron
Jean
J
Julien
Pierre
P
Lamarche
Benoît
B
D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006580:Genetic Carrier Screening; D005820:Genetic Testing; D006801:Humans; D008052:Lipid Metabolism, Inborn Errors / Q000097:blood / Q000235:genetics; D008071:Lipoprotein Lipase / Q000172:deficiency* / Q000235:genetics*; D008077:Lipoproteins, LDL / Q000097:blood / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D015999:Multivariate Analysis; D009154:Mutation / Q000235:genetics*; D011795:Surveys and Questionnaires; D014280:Triglycerides / Q000097:blood
D008077:Lipoproteins, LDL; D014280:Triglycerides; D008071:Lipoprotein Lipase