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薬理と治療
- Authors: Fumiya Kumagai1, et al.
Abstract
Objectives Apolipoprotein(apo)E, one of the main protein constituents of lipoproteins, has the ability of binding to the receptors and plays a role in lipoprotein metabolism. Apo E has genetic polymorphism(E2, E3 and E4). We previously reported that the effects of lipid modifying agents vary depending on the presence or absence of the apo E4 allele. Ezetimibe inhibits cholesterol absorption in the small intestine and reduces plasma LDL cholesterol. The purpose of this study is to clarify the effects of apo E4 allele on plasma LDL cholesterol response to ezetimibe monotherapy in hypercholesterolemic patients. Subjects and Methods Subjects consisted of 16 hypercholesterolemic patients with the apo E3╱3 genotype(8 men, 8 women), and 13 hypercholesterolemic patients with the apo E4 allele (apo E4╱3 genotype: 12 patients; apo E4╱4 genotype: 1 patient)(4 men, 9 women). Subjects took 10 mg of ezetimibe once daily after breakfast. Treatment was continued for 3 months, with fasting blood samples being taken before breakfast in the morning. Results Ezetimibe was administered over 3 months. In the apo E3╱3 group, total cholesterol levels decreased significantly from 236±6 mg╱dL before treatment to 197±7 mg╱dL(percent reduction: -16.2%, P<0.001), and LDL cholesterol levels also decreased significantly from 158±5 mg╱dL before treatment to 124±6 mg╱dL(-21.2%, P<0.001). In the apo E 4 group, total cholesterol levels decreased significantly from 256±7 mg╱dL before treatment to 185±8 mg╱dL(percent reduction: -28.0%, P<0.001); and LDL cholesterol levels also decreased significantly from 168±5 mg╱dL to 103±5 mg╱dL(-38.4%, P<0.001). The percent decrease in total cholesterol before and after ezetimibe treatment was significantly higher in the apo E4 group than in the apo E3╱3 group (-16.2% vs. -28.0%, P<0.001). The percent decrease in LDL cholesterol before and after ezetimibe treatment was significantly higher in the apo E4 group than in the apo E3╱3 group(-21.2% vs. -38.4%, P<0.001). Conclusion This study indicate that the LDL cholesterol-lowering effects of ezetimibe are more effective in individuals who have the apo E4 allele. It is concluded that the apo E4 is one genetic factor regulating the cholesterol-lowering response to ezetimibe.
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