Genetic influences on lipid metabolism trait variability within the Stanislas Cohort

The contribution of 17 polymorphisms within 13 candidate genes on lipid tra it variability was investigated by a multiplex assay in 772 men and 780 wom en coming for a health checkup examination. The studied genes were APOE, AP OB, 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 polyp mo rphisms had a significant effect on lipid traits (P less than or equal to 0 .001 to P less than or equal to 0.01). Genetic effects accounted for 3.5-5. 7% of variation in apolipoprotein B (apoB)-related traits among men, and fo r 5.7-9.0% among women. The contribution of APOE polymorphism on apoB-relat ed traits variability was two to three times more important in women than i n men. We found suggestive evidence for interactive effects between genetic s and age, smoking status, and oral contraceptives. Increase of LDL-cholest erol and apoB concentrations with age was stronger among the epsilon4 carri ers in women, and apolipoprotein A-I (apoA-I) concentration decreased with age in epsilon4 male carriers. The effect of epsilon2 allele on LDL-cholest erol was more important in the oral contraceptive users. In nonsmokers only , the APOC3-1100C allele in women was related to lower apoB-related traits concentrations, and in men to higher apoA-I and HDL-cholesterol concentrati ons. In conclusion, this work, in addition to the reinforcement of the alre ady known associations between APOB, APOE, and APOC3 genes and lipids, lead s to new perspectives in the complex relationships among genes and environm ental factors. The newly observed relationships between E-selectine gene an d lipid concentrations support the hypotheses of multiple metabolic pathway s contributing to the complexity of lipids variability.