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

Variation in apolipoprotein (apo)E genotypes predicts variation in plasma c holesterol and apoB; however, the contest-dependent associations between hi gh density lipoprotein (HDL) cholesterol, apoA-I, triglycerides, and lipopr otein[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, re spectively). The relative frequencies of the epsilon 22, epsilon 32, epsilo n 42, epsilon 33, epsilon 43, and epsilon 44 genotypes were 0.005, 0.127, 0 .027, 0.564, 0.251, and 0.027, respectively. Variations in apoE genotype (i n the order listed above) predicted stepwise increases in cholesterol and a poB 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. I n both genders epsilon 33 individuals had the lowest levels of non-fasting triglycerides, whereas the highest levels were found in individuals with ep silon 22 and epsilon 44 genotypes (both ANOVAs: P < 0.001). Finally, a step wise 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 a nd Lp[a], and variation in apoE genotypes was mainly seen in those with the highest alcohol consumption, similar to the consumption of most men. Varia tions 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. Varia tion 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 plas ma cholesterol and apoB and the variation in apoE genotypes seem invariant, the associations with variation in plasma HDL cholesterol, apoA-I, nonfast ing triglycerides. and Lp[a] seem context dependent.