Apolipoprotein E polymorphism and plasma cholesterol response to probucol.
Probucol has been shown to be an effective and well-tolerated cholesterol-lowering drug. However, response in terms of cholesterol reduction has been shown to vary significantly among individuals. The purpose of this study was to assess the role of apolipoprotein E polymorphism in determining this variation. A retrospective study of 89 hypercholesterolemic type II patients who had been treated with probucol (1 g/d) and for whom the apolipoprotein E phenotype was known was carried out. The patients were first grouped into those with heterozygous familial hypercholesterolemia (FH) and those considered to have other forms of hypercholesterolemia (non-FH). Further subclassification of the individuals in both groups as IIa or IIb, allowed the definition of four diagnostic classes, FH IIa or IIb and non-FH IIa or IIb. Among these classes there was no significant heterogeneity for the relationship between response and age or sex. After correction for between-class heterogeneity in duration of probucol treatment, comparison of individuals with the apo E3/3 phenotype with those carrying the epsilon 4 allele showed significant differences in cholesterol reduction both absolute change and percent change. Further contrasts between diagnostic and apo E genotype stratifications of these data showed that the FH patients carrying the epsilon 4 allele had the greatest reduction in cholesterol level.
D000328:Adult; D000483:Alleles; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics*; D002784:Cholesterol / Q000097:blood*; D005838:Genotype; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy*; D008875:Middle Aged; D010636:Phenols / Q000494:pharmacology*; D011110:Polymorphism, Genetic; D011341:Probucol / Q000494:pharmacology*; D012189:Retrospective Studies
D001057:Apolipoproteins E; D010636:Phenols; D002784:Cholesterol; D011341:Probucol