Abstract
An increasing number of studies have investigated the association between SLCO1B1 −521T>C and −388A>G polymorphisms and the risk of statin-induced adverse drug reactions (ADRs), but the results have been inconsistent. This meta-analysis was performed to gain more insight into the relationship. PubMed, Embase, Cochrane Library and Web of Science were searched for relevant articles published before March 5th, 2015. The quality of included studies was evaluated by the Newcastle-Ottawa Quality scale. Pooled effect estimates (odds ratios [ORs] or hazard ratios [HRs) and corresponding 95 % confidence intervals (CIs) were calculated to assess the association in overall and subgroup analyses for various genetic models. Begg’s rank correlation test and Egger’s linear regression test were used to examine the publication bias. A total of nine cohort and four case–control studies involving 11, 246 statin users, of whom 2, 355 developing ADRs were included in the analysis. Combined analysis revealed a significant association between the SLCO1B1−521T>C polymorphism and increased risk for ADRs caused by various statins, but the synthesis heterogeneity was generally large (dominant model: pooled effect estimate = 1.85, 95 % CI 1.20–2.85, P = 0.005; I2 = 80.70 %, Pheterogeneity < 0.001). Subgroup analysis by statin type showed that the ADRs risk was significantly elevated among simvastatin users (dominant model: pooled effect estimate = 3.43, 95 % CI 1.80–6.52, P = 0.001; I2 = 59.60 %, Pheterogeneity = 0.060), but not among atorvastatin users. No significant relationship was found between the −388A>G polymorphism and ADRs caused by various statins (dominant model: pooled effect estimate = 0.94, 95 % CI 0.79–1.13, P = 0.526; I2 = 40.10 %, Pheterogeneity = 0.196). The meta-analysis suggests that SLCO1B1 −521T>C polymorphism may be a risk factor for statin-induced ADRs, especially in simvastatin therapy. Conversely, there may be no significant association for −388A>G polymorphism.
Highlights
Statins or the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have become the most important pharmaceutical intervention for the primaryJiang et al SpringerPlus (2016) 5:1368Link et al 2008; Thompson et al 2006)
Studies were considered eligible if they met all of the following criteria: (1) It investigated the association between −521T>C or −388A>G polymorphisms in the SLCO1B1 gene and the risk of statininduced adverse drug reactions (ADRs); (2) It provided effect estimates (OR, RR, or Hazard ratio (HR)) and their corresponding 95 % confidence intervals or allele or genotype frequencies for calculating the effect estimates; (3) The publication language was English
Recent studies showed that genetic variants in the SLCO1B1 gene modified the risk of statin-induced myopathy, but the results were controversial
Summary
Statins or the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have become the most important pharmaceutical intervention for the primaryJiang et al SpringerPlus (2016) 5:1368Link et al 2008; Thompson et al 2006). The SLCO1B1 gene locates on the chromosome 12 (Chr 12p12.2) occupying 109 kb, which encodes the organic anion transporting polypeptide 1B1 (OATP1B1) This is an influx transporter expressed on the sinusoidal membrane of human hepatocytes and facilitates the liver uptake of most statins (atorvastatin, rosuvastatin, pravastatin, simvastatin, and lovastatin) (Pasanen et al 2007; König et al 2006; Pasanen et al 2006; Chen et al 2008). An increasing number of studies began to explore the role of SLCO1B1 polymorphisms in statin-induced ADRs. the results remain inconsistent and with limited power (Link et al 2008; de Keyser et al 2014; Marciante et al 2011; Voora et al 2009; Danik et al 2013; Donnelly et al 2011; Carr et al 2013; Santos et al 2012; Brunham et al 2012)
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