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 tota l cholesterol (TC) and LDL cholesterol (LDL-C) differed between apolip oprotein E (APOE) genotypes epsilon 3 epsilon 3 and epsilon 3 epsilon 4, 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 epsilon 3 epsilon 3 and epsilon 3 epsi lon 4 APOE genotypes, over three exams, was reanalyzed. Additionally, the change in triglycerides (TG) and in HDL-cholesterol (HDL-C), betwe en the epsilon 3 epsilon 3 and epsilon 3 epsilon 4 APOE genotypes-as w ell as the differences between the epsilon 3 epsilon 3 and epsilon 3 e psilon 2 genotypes, for TC, LDL-C, TG, and HDL-C-were contrasted over the three exams. At exam 1 TG was higher in the epsilon 3 epsilon 4 gr oup than in the epsilon 3 epsilon 3 group (mean age 48 years), and at exams 2 and exam 3 (mean ages 58 and 63 years, respectively) it was si milar (P =.009 for the exam-by-genotype-interaction effect in the repe ated-measures analysis). A similar trend was seen for TC (P =.03), yet previously detected LDL-C effects were not apparent (P =.46). Those w ith the epsilon 3 epsilon 2 genotype had higher TG and lower LDL-C and TC at each exam than were seen in those with the epsilon 3 epsilon 3 genotype, although the differences in the values were not always stati stically significant. Differences in TC, LDL-C, and TG, between the ep silon 3 epsilon 2-genotype and epsilon 3 epsilon 3-genotype groups, di d not significantly change over the three exams. HDL-C levels were rel atively stable over the exams; however, the exam-by-genotype interacti on was significant for the epsilon 3 epsilon 2 genotype versus the eps ilon 3 epsilon 3 genotype (P =.02). The epsilon 4 allele effects on TG and TC changed between longitudinal exams and may be age dependent. C hanges, with age, in the effect of the epsilon 3 epsilon 4 genotype on lipids may impact the risk of developing atherosclerotic disease.