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Journal of Lipid Research, Vol. 42, 1879-1890, November 2001
Copyright © 2001 by Lipid Research, Inc.

Genetic influences on lipid metabolism trait variability within the Stanislas Cohort

C. Pallauda, R. Gueguenb, C. Sassa, M. Growc, S. Chengc, G. Siesta, and S. Visvikisa
a Institut National de la Sante et de la Recherche Médicale (INSERM) U525, 2 Avenue du Doyen Jacques Parisot, 54501 Vandoeuvre-lès-Nancy, France–Université Henri Poincaré, Nancy I, 30 Rue Lionnois, 54000 Nancy, France
b Centre de Médecine Préventive, 2 Avenue du Doyen Jacques Parisot, 54501 Vandoeuvre-lès-Nancy, France–Université Henri Poincaré, Nancy I, 30 Rue Lionnois, 54000 Nancy, France
c Department of Human Genetics, Roche Molecular Systems, Inc., Alameda, CA

Correspondence to: S. Visvikis, To whom correspondence should be addressed., Sophie.Visvikis{at}cmp.u-nancy.fr (E-mail)

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 polymorphisms 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 {varepsilon}4 carriers in women, and apolipoprotein A-I (apoA-I) concentration decreased with age in {varepsilon}4 male carriers. The effect of {varepsilon}2 allele on LDL-cholesterol 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 concentrations.

In conclusion, this work, in addition to the reinforcement 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 between E-selectine gene and lipid concentrations support the hypotheses of multiple metabolic pathways contributing to the complexity of lipids variability. — Pallaud, C., R. Gueguen, C. Sass, M. Grow, S. Cheng, G Siest, and S. Visvikis. Genetic influences on lipid metabolism trait variability within the Stanislas Cohort. J. Lipid Res. 2001. 42: 1879–1890.

Supplementary key words: lipid variability, candidate genes, healthy population, polymorphism


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