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 (apo) 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 (apo 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.
Ordovas
J M
JM
Lipid Metabolism Laboratory, USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.
Lopez-Miranda
J
J
Perez-Jimenez
F
F
Rodriguez
C
C
Park
J S
JS
Cole
T
T
Schaefer
E J
EJ
D000483:Alleles; D001054:Apolipoproteins A / Q000097:blood / Q000235:genetics*; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics*; D004311:Double-Blind Method; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000097:blood; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D008077:Lipoproteins, LDL / Q000097:blood / Q000187:drug effects* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D017035:Pravastatin / Q000627:therapeutic use*
D001054:Apolipoproteins A; D001057:Apolipoproteins E; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; C022205:apolipoprotein A-IV; D006903:Hydroxymethylglutaryl CoA Reductases; D017035:Pravastatin