Influence of apolipoprotein E polymorphism on bezafibrate treatment response in dyslipidemic patients

To examine the significance of apolipoprotein E (apo E) polymorphism in the hypolipidemic effect of bezafibrate, we evaluated the influence of different apo E phenotypes on serum lipid response to bezafibrate treatment in 58 dyslipidemic patients with WHO phenotypes of IIb, IV, or isolated hypo HDL cholesterolemia. Patients were categorized into one of three groups according to apo E phenotypes of E2 (E2/3, n=5), E3 (E3/3, n=35), and E4 (E3/4 and E4/4, n=18). After 3 months daily administration of 400 mg bezafibrate, serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC) levels changed on average in the E3 group [-8.0%; p<0.05 and +1.1%; not significant (ns), respectively], the E2 group (-18.3%; p<0.005 and -26.9%; p<0.05, respectively) and the E4 group (+3.8%; ns and +10.1%; ns, respectively). The changes in TC and LDLC levels in the E4 group was significantly less effective compared with those in the E3 (p<0.05) and E2 groups (p<0.01). Bezafibrate induced a reduction in serum triglyceride (TG) levels in the E3 group (-50.1%; p<0.0001), the E2 group (-46.9%; p<0.05) and the E4 group (-44.8%; p<0.005). An increase in high-density lipoprotein cholesterol (HDLC) levels was also observed in the E3 group (+27.5%; p<0.0001), the E2 group (+35.0%; ns) and the E4 group (+38.8%; p<0.005). However, there was no significant difference in the changes of TG and HDLC levels between the groups. These results suggest an important role of apo E polymorphism in modulating serum lipid response to bezafibrate, and phenotyping of apo E helps predict the therapeutic effect of bezafibrate treatment.