APOLIPOPROTEIN-E POLYMORPHISM AND HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA - SEX-SPECIFIC EFFECTS

The impact of apolipoprotein (apo) E polymorphism on interindividual variation in plasma lipid, lipoprotein, and apolipoprotein levels was studied in a sample of familial hypercholesterolemic (FH) patients (147 women, 116 men) with the same mutation, a > 10-kilobase deletion of the low-density lipoprotein (LDL) receptor gene. Each trait was adjusted for concomitants (age, age squared, height, weight, weight squared) for each sex separately before the apoE genotypic effects were estimated. The relative contribution of concomitants to sample variability was found to be very different in women and in men. Allelic variation in the apoE gene was shown to explain a statistically significant portion of the variability in adjusted lipid traits. Moreover, the contribution of apoE polymorphism was different between sexes. In women, there was significant variability (P < .01) among apoE genotypes for total cholesterol, LDL cholesterol, and total and LDL apoB. In men, significant variability (P < .01) was observed among apoE genotypes in very-low-density lipoprotein (VLDL) cholesterol and triglyceride levels. Women with the epsilon 3/2 genotype had significantly lower means for total cholesterol, LDL cholesterol, and LDL apoB than women with the epsilon 3/3 genotype (P < .05). In men, the mean VLDL cholesterol was significantly higher for the epsilon 2/2 genotype and was significantly lower for the epsilon 4/2 genotype than the mean for the epsilon 3/3 genotype (P < .05). Overall, the greatest influence was associated with the epsilon 2 allele, and the LDL cholesterol-lowering effect of this allele was present only in FH women. No statistically significant apoE effect was shown on lipoprotein(a) levels in either sex. Less than 20% of the variability for any of the lipid traits among FH patients with the > 10-kb deletion is explained by the predictors considered in this study. Most of the remaining Variability in lipid traits must be explained by other genetic or environmental factors. In conclusion, this study documents large effects of the epsilon 2 allele and the sex-specific apoE genotype influence in a large sample of FH patients with the same LDL receptor mutation.