Yaming Du, Sizheng Wang, Zhangyong Chen, Shusen Sun, Zhigang Zhao* and Xingang Li* Pages 4044 - 4050 ( 7 )
Background: 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.
Aim: This study aimed to investigate the association between SLCO1B1 polymorphisms (c.521T>C or c.388A>G) and atorvastatin safety and efficacy.
Methods: 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.
Results: 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).
Conclusion: SLCO1B1 c.521T>C polymorphism is a valuable biomarker for the evaluation of atorvastatin safety and efficacy.
SLCO1B1, atorvastatin, safety, lipid-lowering effects, meta-analysis, statin.
College of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, College of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, College of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, College of Pharmacy and Health Sciences, Western New England University, Springfield, Massachusetts 000191, Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing