Department of Pharmacy, Peking University First Hospital, Beijing, China.
Pharmacogenet Genomics. 2018 Dec;28(12):261-267. doi: 10.1097/FPC.0000000000000356.
OBJECTIVE: The aim of this study was to determine the impact of the SLCO1B1, apolipoprotein E (ApoE), and CYP2C9 genotypes on the lipid-lowering efficacy of fluvastatin. METHODS: We performed electronic searches on the PubMed, Embase, and Cochrane Library databases to identify studies published through October 2017. Studies that reported the effect estimates with 95% confidence intervals (CIs) of total cholesterol (TC), triglyceride, low-density lipoprotein (LDL), and high-density lipoprotein were included so that the different genotype categories could be compared. Weighted mean difference (WMD) was used to summarize the effect estimates. RESULTS: Six studies, involving a total of 1171 individuals, were included in the final analysis. We noted that the patient carrier SLCO1B1 521TT was associated with greater change in TC (WMD: -2.98; 95% CI: -5.12 to -0.84; P=0.006) and LDL (WMD: -5.58; 95% CI: -10.64 to -0.52; P=0.031) compared with 521TC or CC. Furthermore, the patient carrier ApoE*2/3 showed more change in high-density lipoprotein compared with ApoE3/3 (WMD: 18.76; 95% CI: 8.97-28.55; P<0.001) and ApoE3/*4 or *4/*4 (WMD: 22.51; 95% CI: 0.98-44.04; P=0.040). Finally, the CYP2C9 genotypes showed no correlation with the effects of fluvastatin on TC, triglyceride, and LDL. CONCLUSION: The findings of this study suggested that the SLCO1B1 and ApoE polymorphisms could influence the lipid-lowering effect of fluvastatin, whereas the CYP2C9 genotypes were not associated with the therapeutic effects of fluvastatin.
目的:本研究旨在确定 SLCO1B1、载脂蛋白 E(ApoE)和 CYP2C9 基因型对氟伐他汀降脂疗效的影响。
方法:我们对 PubMed、Embase 和 Cochrane 图书馆数据库进行了电子检索,以确定截至 2017 年 10 月发表的研究。纳入报告总胆固醇(TC)、甘油三酯、低密度脂蛋白(LDL)和高密度脂蛋白的效应估计值和 95%置信区间(CI)的研究,以便比较不同基因型类别。使用加权均数差(WMD)来总结效应估计值。
结果:最终分析纳入了 6 项研究,共 1171 人。我们注意到,患者携带 SLCO1B1 521TT 与 TC(WMD:-2.98;95%CI:-5.12 至-0.84;P=0.006)和 LDL(WMD:-5.58;95%CI:-10.64 至-0.52;P=0.031)的变化更大。此外,与 ApoE*3/3 相比,患者携带 ApoE2/3 对高密度脂蛋白的变化更大(WMD:18.76;95%CI:8.97-28.55;P<0.001)和 ApoE3/*4 或 *4/*4(WMD:22.51;95%CI:0.98-44.04;P=0.040)。最后,CYP2C9 基因型与氟伐他汀对 TC、甘油三酯和 LDL 的作用无关。
结论:本研究结果表明,SLCO1B1 和 ApoE 多态性可能影响氟伐他汀的降脂作用,而 CYP2C9 基因型与氟伐他汀的治疗效果无关。
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