The response to lovastatin treatment in patients with heterozygous familial hypercholesterolemia is modulated by apolipoprotein E polymorphism.
In a retrospective study, we examined the influence of apolipoprotein (apo) E polymorphism and gender on the response to treatment with 80 mg/d lovastatin in a homogeneous population of patients with familial hypercholesterolemia (FH), most of whom were carriers of the 10-kb deletion of the low-density lipoprotein (LDL) receptor gene. Apo E phenotype distribution among the 189 FH patients was not different from that of a normal population sample. The total and LDL cholesterol (LDL-C) response to lovastatin in the overall group (men and women) was significantly lower in the E4 subset compared with E2 and E3 subsets. This finding is in agreement with trends observed in previous reports. On the other hand, the response of LDL-C to lovastatin was significantly lower in E4 men than in E4 women, whereas the high-density lipoprotein cholesterol (HDL-C) concentration in the E4 group increased significantly more in men than in women, suggesting a role of gender in modulating the response to lovastatin. Hence, apo E polymorphism influenced LDL-C (and HDL-C) response to lovastatin in men, but not in women, revealing the existence of a gene-by-gender interaction. These findings were independent of the nature of the LDL receptor defect. We conclude that male FH patients carrying the epsilon 4 allele respond less efficiently to lovastatin than men carrying the epsilon 3 or epsilon 2 allele or women of any apo E phenotype with respect to decreasing total cholesterol and LDL-C levels, but respond more efficiently with respect to increasing HDL-C levels. The full practical implication of these findings remains to be explored.
Carmena
R
R
Hospital Clinico Universitario, Endocrine Service, Valencia, Spain.
Roederer
G
G
Mailloux
H
H
Lussier-Cacan
S
S
Davignon
J
J
D000328:Adult; D001057:Apolipoproteins E / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D008055:Lipids / Q000097:blood; D008148:Lovastatin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D011973:Receptors, LDL / Q000235:genetics; D012189:Retrospective Studies
D001057:Apolipoproteins E; D008055:Lipids; D011973:Receptors, LDL; D008148:Lovastatin