Effect of apolipoprotein E polymorphism and XbaI polymorphism of apolipoprotein B on response to lovastatin treatment in familial and non-familial hypercholesterolaemia.
Despite the well-documented efficacy of lovastatin, a wide inter-individual variation in treatment responses has been observed. The aim of the present study was to investigate the possible roles of apolipoprotein E (apo E) phenotype and apolipoprotein B (apo B) XbaI genotype on this variation. The apo E phenotype was determined in 232 subjects (78 cases of familial hypercholesterolaemia [FH] and 154 cases of non-familial hypercholesterolaemia [non-FH]) and the apo B XbaI genotype was determined in 211 subjects (67 cases of FH, 144 cases of non-FH). Depending on their baseline total serum cholesterol levels, these patients used a starting dose of lovastatin of either 20 or 40 mg nightly. After 6 weeks of therapy, slightly but significantly smaller reductions in LDL-cholesterol were observed in patients with the E4/3 phenotype compared with those with the E3/3 phenotype in non-FH with lovastatin 20 mg (-20 vs. -28%; P = 0.043) and in total cholesterol in FH with lovastatin 40 mg (-23 vs. -27%; P = 0.023). No significant differences were found in non-FH patients starting with lovastatin, 40 mg. After doubling of the lovastatin doses, all treatment responses became similar among apo E phenotypes. Moreover, when all patients using lovastatin 40 mg either at 6 or 12 weeks were pooled (n = 224), no differences in treatment responses were observed between the E3/2, E3/3, E4/3 and E4/4 phenotypes. The apo B XbaI genotype did not affect the hypocholesterolaemic efficacy of lovastatin in any of the patient groups. Thus our results indicate that inter-individual variation in the treatment response to lovastatin in both familial and non-familial hypercholesterolaemia is mainly due to factors other than the apo E phenotype or apo B XbaI genotype.
First Department of Medicine, University of Helsinki, Finland.
J P
JP
Ojala
E
E
Helve
C
C
Ehnholm
K
K
Aalto-Setälä
K K
KK
Kontula
M J
MJ
Tikkanen
D000328:Adult; D000368:Aged; D001055:Apolipoproteins B / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D015252:Deoxyribonucleases, Type II Site-Specific; D005260:Female; D005838:Genotype; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy*; D008148:Lovastatin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic
D001055:Apolipoproteins B; D001057:Apolipoproteins E; D008148:Lovastatin; C025580:endodeoxyribonuclease XBAI; D015252:Deoxyribonucleases, Type II Site-Specific