Context-dependent and invariant associations between lipids, lipoproteins, and apolipoproteins and apolipoprotein E genotype

Variation in apolipoprotein (apo)E genotypes predicts variation in plasma cholesterol and apoB; however, the context-dependent associations between high density lipoprotein (HDL) cholesterol, apoA-I, triglycerides, and lipoprotein[a] (Lp[a]) and this polymorphism remain unsettled. We genotyped 5,025 women and 4,035 men sampled to represent a white general population in the age range 20 to 80+ years (mean ages 58 and 57 years for women and men, respectively). The relative frequencies of the ε22, ε32, ε42, ε33, ε43, and ε44 genotypes were 0.005, 0.127, 0.027, 0.564, 0.251, and 0.027, respectively. Variations in apoE genotype (in the order listed above) predicted stepwise increases in cholesterol and apoB in both genders (all ANOVAs: P < 0.001), and stepwise decreases in HDL cholesterol and apoA-I in women (both ANOVAs: P < 0.001), but not in men. In both genders ε33 individuals had the lowest levels of nonfasting triglycerides, whereas the highest levels were found in individuals with ε22 and ε44 genotypes (both ANOVAs: P < 0.001). Finally, a stepwise increase in Lp[a] was seen in women (ANOVA: P < 0.001), but not in men. In women, the association between variation in nonfasting triglycerides and Lp[a], and variation in apoE genotypes was mainly seen in those with the highest alcohol consumption, similar to the consumption of most men. Variations in apoE genotype predicted 5% and 11% in women, and 2% and 6% in men, of the total variation in plasma cholesterol and apoB, respectively. Variation in levels of plasma lipoproteins is associated with variation in apoE genotypes in the population at large, with the most pronounced association in women, except for nonfasting triglycerides, for which the association is most pronounced in men. Whereas the associations between variation in plasma cholesterol and apoB and the variation in apoE genotypes seem invariant, the associations with variation in plasma HDL cholesterol, apoA-I, nonfasting triglycerides, and Lp[a] seem context dependent.—Frikke-Schmidt, R., B. G. Nordestgaard, B. Agerholm-Larsen, P. Schnohr, and A. Tybjærg-Hansen. Context-dependent and invariant associations between lipids, lipoproteins, and apolipoproteins and apolipoprotein E genotype. J. Lipid Res. 2000. 41: 1812–1822.