EFFECT OF APOLIPOPROTEIN-E AND A-IV PHENOTYPES ON THE LOW-DENSITY-LIPOPROTEIN RESPONSE TO HMG COA REDUCTASE INHIBITOR THERAPY

Our purpose was to assess the effect of apolipoprotein (ape) E and apo A-IV isoform variation on low density lipoprotein (LDL) cholesterol lowering response to the HMG CoA reductase inhibitor, pravastatin, plasma samples were obtained from participants (ape E, n = 97; apo A-IV, n = 144) in the PLAC-I (Pravastatin Limitation of Atherosclerosis in Coronary Arteries Study-1), The mean LDL cholesterol reduction in these subjects who were randomized to pravastatin 40 mg/day was 28%. Subjects with the APOE*2 allele (n = 12) had significantly (P = 0.04) greater reductions at 36% than subjects homozygous for the APOE*3 allele (n = 66, 27%) or those with the APOE*4 allele (n = 19, 26%), No significant effect of apo A-IV phenotype on LDL cholesterol lowering in response to pravastatin was noted, A meta-analysis utilizing published data from 4 previously published studies as well as our own data with a total sample size of 625 subjects was carried out, This analysis indicates that the presence of the APOE*2 allele was associated with a significantly greater (P < 0.05) LDL-cholesterol lowering response at 37% than those subjects homozygous for the APOE*3 allele at 35%, while those with the APOE*4 allele had a significantly lower response (P < 0.05), at 33%. These data are consistent with the concept that apo E phenotype modulates the LDL cholesterol lowering response observed with the use of HMG CoA reductase inhibitors.