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Beneficial effect of ezetimibe-atorvastatin combination therapy in patients with a mutation in ABCG5 or ABCG8 gene.

Lipids Health Dis. 2020 Jan 04;19(1):3
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摘要


BACKGROUND:Use of ezetimibe on top of statin therapy has been shown to be effective to reduce LDL cholesterol level in hypercholesterolemic patients. However, little is known regarding the individual variety of the effectiveness of ezetimibe. We hypothesized that hypercholesterolemic patients with a mutation in ABCG5 or ABCG8 gene exhibit better response to ezetimibe than those without, based on the fact that ezetimibe is hyper-effective for in patients with sitosterolemia caused by ABCG5 or ABCG8 genetic mutations. METHODS:Electronical medical record were reviewed in a total of 321 hypercholesterolemic patients (baseline LDL cholesterol = 192 ± 46 mg/dl) prescribed ezetimibe 10 mg daily on top of atorvastatin 10 mg daily who had undergone genetic analysis of ABCG5 or ABCG8 gene in our institute since 2006 to 2017. Pathogenicity of the variants were determined using standard variant filtering schema, including minor allele frequency, in silico annotation tools. Patients were divided into 2 groups based on the presence of ABCG5 or ABCG8 mutation. We compared the percent reduction of LDL cholesterol as well as the achieved LDL cholesterol levels between these 2 groups. RESULTS:We found 26 (8%) individuals who exhibit deleterious mutations in ABCG5 or ABCG8 gene. Baseline characteristics under the atorvastatin 10 mg therapy were comparable in age, gender, and LDL cholesterol level between 2 groups. Under these conditions, percent reduction of LDL cholesterol in mutation positive group was significantly larger than that of mutation negative group (28 ± 16% vs. 39 ± 21%, p < 0.05). As a result, the achieved LDL cholesterol level in mutation positive group was significantly lower than that of mutation negative group (87 ± 29 mg/dl vs. 72 ± 26% mg/dl, p < 0.05). CONCLUSION:These results suggest that ezetimibe-atorvastatin combination therapy might be more beneficial in hypercholesterolemic patients with a mutation in ABCG5 or ABCG8 gene.

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