Genetic influences on lipid metabolism trait variability within the Stanislas Cohort.

The contribution of 17 polymorphisms within 13 candidate genes on lipid trait variability was investigated by a multiplex assay in 772 men and 780 women coming for a health checkup examination. The studied genes were APOE, APOB, APOC3, CETP, LPL, PON, MTHFR, FGB, GpIIIa, SELE, ACE, and AGT. We found that APOB-Thr71Ile, APOE-(112/158), APOC3-1100C/T, and SELE-98G/T poly- morphisms had a significant effect on lipid traits ( P < 0.001 to P < 0.01). Genetic effects accounted for 3.5-5.7% of variation in apolipoprotein B (apoB)-related traits among men, and for 5.7-9.0% among women. The contribution of APOE polymorphism on apoB-related traits variability was two to three times more important in women than in men. We found suggestive evidence for interactive effects between genetics and age, smoking status, and oral contraceptives. Increase of LDL-cholesterol and apoB concentrations with age was stronger among the « 4 carriers in women, and apo- lipoprotein A-I (apoA-I) concentration decreased with age in « 4 male carriers. The effect of « 2 allele on LDL-cholesterol was more important in the oral contraceptive users. In non- smokers only, the APOC3-1100C allele in women was re- lated to lower apoB-related traits concentrations, and in men to higher apoA-I and HDL-cholesterol concentra- tions. In conclusion, this work, in addition to the rein- forcement of the already known associations between APOB, APOE, and APOC3 genes and lipids, leads to new perspectives in the complex relationships among genes and environmental factors. The newly observed relationships be- tween E-selectine gene and lipid concentrations support the hypotheses of multiple metabolic pathways contributing to the complexity of lipids variability. —Pallaud, C., R. Gue- guen, C. Sass, M. Grow, S. Cheng, G Siest, and S. Visvikis. Ge- netic influences on lipid metabolism trait variability within the Stanislas Cohort. J. Lipid Res. 2001. 42: 1879-1890.