Evidence that the apolipoprotein E-genotype effects on lipid levels can change with age in males: A longitudinal analysis

We previously reported that change, with age, in plasma levels of total cholesterol (TC) and LDL cholesterol (LDL-C) differed between apolipoprotein E (APOE) genotypes ε3ε3 and ε3ε4, in a sample of 77 older, unrelated males. By use of a larger sample from that cohort, followed longitudinally during 1969-87, the change in TC and in LDL-C, between the ε3ε3 and ε3ε4 APOE genotypes, over three exams, was reanalyzed. Additionally, the change in triglycerides (TG) and in HDL-cholesterol (HDL-C), between the ε3ε3 and ε3ε4 APOE genotypes-as well as the differences between the ε3ε3 and ε3ε2 genotypes, for TC, LDL-C, TG, and HDL-C-were contrasted over the three exams. At exam 1 TG was higher in the ε3ε4 group than in the ε3ε3 group (mean age 48 years), and at exams 2 and exam 3 (mean ages 58 and 63 years, respectively) it was similar (P = .009 for the exam-by-genotype-interaction effect in the repeated-measures analysis). A similar trend was seen for TC (P = .03), yet previously detected LDL-C effects were not apparent (P = .46). Those with the ε3ε2 genotype had higher TG and lower LDL-C and TC at each exam than were seen in those with the ε3ε3 genotype, although the differences in the values were not always statistically significant. Differences in TC, LDL-C, and TG, between the ε3ε2-genotype and ε3ε3- genotype groups, did not significantly change over the three exams. HDL-C levels were relatively stable over the exams; however, the exam-by-genotype interaction was significant for the ε3ε2 genotype versus the ε3ε3 genotype (P = .02). The ε4 allele effects on TG and TC changed between longitudinal exams and may be age dependent. Changes, with age, in the effect of the ε3ε4 genotype on lipids may impact the risk of developing atherosclerotic disease.