Association between SLCO1B1 −521T>C and −388A>G polymorphisms and risk of statin-induced adverse drug reactions: A meta-analysis

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.

Effect of SLCO1B1 T521C on Statin-induced Myotoxicity: A Systematic Review and Meta-analysis

“…Despite the differences in the studies included in each metaanalysis, the results of this study coincide with the results of the previous meta-analysis by Hoe et al Similarly, Jiang et al reported 1.85 times higher risk for statin associated adverse drug reactions in the carriers of the 521C allele than in the 521TT carriers. 45) These results are supported those of the pharmacokinetic studies in which the 521C allele was associated with a significantly increased statin AUC. 19,43) There are some limitations in this meta-analysis.…”

Organic Anion Transporting Polypeptides: Emerging Roles in Cancer Pharmacology

“…OATP1B1. SLCO1B1 variants have been widely studied with regard to impact on the pharmacokinetics of many drugs (Niemi et al, 2011;Shitara, 2011), and notably in the incidence of adverse drug reactions in patients treated with statins (Link et al, 2008;Jiang et al, 2016). The SLCO1B1 c.521T.C variant, which has a minor allele frequency of 12%-18% in European and East Asian populations with lower frequency (1.9%) in sub-Saharan African populations (Pasanen et al, 2008), has been the most extensively studied of the SLCO1B1 variants and is associated with significantly impaired hepatic uptake, and thus corresponding increased plasma levels, of many substrates (Tirona et al, 2001;Nishizato et al, 2003;Mwinyi et al, 2004;Niemi et al, 2004Niemi et al, , 2005aKameyama et al, 2005;Nozawa et al, 2005a;Katz et al, 2006;Ho et al, 2007;Zhang et al, 2007;Xiang et al, 2009).…”

“…The SLCO1B1 c.521T.C variant, which has a minor allele frequency of 12%-18% in European and East Asian populations with lower frequency (1.9%) in sub-Saharan African populations (Pasanen et al, 2008), has been the most extensively studied of the SLCO1B1 variants and is associated with significantly impaired hepatic uptake, and thus corresponding increased plasma levels, of many substrates (Tirona et al, 2001;Nishizato et al, 2003;Mwinyi et al, 2004;Niemi et al, 2004Niemi et al, , 2005aKameyama et al, 2005;Nozawa et al, 2005a;Katz et al, 2006;Ho et al, 2007;Zhang et al, 2007;Xiang et al, 2009). The c.521T.C variant has been identified as a significant risk factor for statininduced myopathy (Link et al, 2008) and other statin-induced adverse drug reactions (Jiang et al, 2016). A case-control analysis of patients in a large randomized trial study on the effectiveness of additional reductions in cholesterol and homocysteine found an odds ratio for myopathy of 4.5 per copy of the variant C allele, and homozygous variant (CC) patients had an odds ratio of 16.9 for development of myopathy compared with TT patients (Link et al, 2008).…”

Polymorphism analysis of APOE and SLCO1B1 genes in Meizhou area of southern China

“…The non-coding SLCO1B1 388A>G (rs2306283) and 521T>C (rs4149056) single nucleotide polymorphism have been shown to be significantly related gene to statin-induced ADRs (Jiang et al, 2017;Jiang et al, 2016). Patients carried 521C allele (located in exon 4) had reduced hepatic uptake and increases the concentration of statins in blood, which might increase the ADRs risk and the A388G allele may be associated with reduced statin bioavailability (Nies et al, 2013).…”