College of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China.
Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Curr Pharm Des. 2018;24(34):4044-4050. doi: 10.2174/1381612825666181219163534.
Atorvastatin is the best-selling statin in the market. However, some patients have to reduce drug doses or discontinue atorvastatin therapy mainly due to adverse drug reactions (ADRs). Genetic factors play an important role in the occurrence of ADRs.
This study aimed to investigate the association between SLCO1B1 polymorphisms (c.521T>C or c.388A>G) and atorvastatin safety and efficacy.
We systematically searched PubMed, Web of Science and Embase to screen relevant studies published before Sep 2018. This meta-analysis was performed to identify the relationship between SLCO1B1 c.521T>C or c.388A>G polymorphisms and atorvastatin-related ADRs by the odds ratios (ORs) and 95% confidence intervals (CIs). The relationship of SLCO1B1 polymorphisms and lipid-lowering effects [low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC)] was assessed in pooled data by calculating the mean difference (MD) with 95% CIs. All statistical tests were performed by the Review Manager 5.3 software.
A total of 13 studies involving 1,550 atorvastatin users were included in this analysis. There was a significant association between the SLCO1B1 c.521T>C polymorphism and atorvastatin-related ADRs associated with risk allele C (dominant model: OR=1.57, P=0.01). Allele C is associated with increased lipid-lowering efficacy in people with Hyperlipidemias as compared to allele T (LDL-C/dominant model: MD=6.19, P<0.00001 and (TC)/dominant model: MD=2.07, P=0.008). No association between the SLCO1B1 c.388A>G polymorphism and ADRs or efficacy was observed (P>0.05).
SLCO1B1 c.521T>C polymorphism is a valuable biomarker for the evaluation of atorvastatin safety and efficacy.
阿托伐他汀是市场上最畅销的他汀类药物。然而，由于不良反应（ADR），一些患者不得不减少药物剂量或停止阿托伐他汀治疗。遗传因素在 ADR 的发生中起着重要作用。
本研究旨在探讨 SLCO1B1 多态性（c.521T>C 或 c.388A>G）与阿托伐他汀安全性和疗效的关系。
我们系统地检索了 PubMed、Web of Science 和 Embase，以筛选 2018 年 9 月前发表的相关研究。通过优势比（OR）和 95%置信区间（CI），采用荟萃分析来确定 SLCO1B1 c.521T>C 或 c.388A>G 多态性与阿托伐他汀相关 ADR 之间的关系。通过计算均数差（MD）和 95%CI 来评估 SLCO1B1 多态性与降脂作用[低密度脂蛋白胆固醇（LDL-C）、总胆固醇（TC）]之间的关系。所有统计检验均采用 Review Manager 5.3 软件进行。
本分析共纳入 13 项研究，共 1550 例阿托伐他汀使用者。SLCO1B1 c.521T>C 多态性与阿托伐他汀相关 ADR 与风险等位基因 C 显著相关（显性模型：OR=1.57，P=0.01）。与等位基因 T 相比，等位基因 C 与高脂血症患者的降脂疗效增加相关（LDL-C/显性模型：MD=6.19，P<0.00001 和（TC）/显性模型：MD=2.07，P=0.008）。未观察到 SLCO1B1 c.388A>G 多态性与 ADR 或疗效之间存在关联（P>0.05）。
SLCO1B1 c.521T>C 多态性是评估阿托伐他汀安全性和疗效的有价值的生物标志物。
