Meta-Analysis of the SLCO1B1 c.521T>C Variant Reveals Slight Influence on the Lipid-Lowering Efficacy of Statins

Abstract

BackgroundSeveral studies have focused on the association between the lipid-lowering efficacy of statins and the SLCO1B1 c.521T>C polymorphism; however, the results are conflicting. The effects of statins show significant variability between individuals. This meta-analysis aimed to investigate the effects of the SLCO1B1 c.521T>C polymorphism on the lipid-lowering effects of statins.MethodsWe systematically searched PubMed and Web of Science to screen relevant studies. Meta-analysis was performed to identify the association between SLCO1B1 c.521 polymorphisms and the lipid-lowering effects of statinson the basis of the standard mean difference (SMD) and 95% confidence intervals (CIs). Additionally, we checked for heterogeneity (I2) among studies and evidence of publication bias. We obtained eight studies including 2,012 wild genotype (T/T) and 526 variant genotype (T/C and C/C) cases.ResultsNo significant difference was observed in the lipid-lowering efficacy of statins between the wildand variant genotypes of SLCO1B1, with a pooled SMD of 0.03 (95% CI: -0.07-0.13). Furthermore, there was no significant effect in the meta-analyses of the variant heterozygote, homozygote, and Chinese populations. Subgroup meta-analysis indicated that the timerequired for the statin to take effectdid notsignificantly affect the association between lipid-lowering efficacy of statins and SLCO1B1 c.521T>C polymorphism. However, thewild genotype improved the lipid-lowering efficacy of simvastatin with a pooled SMD of -0.26 (95% CI: -0.47- -0.05).ConclusionsNo significant association was detected between the lipid-lowering efficacy of statins and the SLCO1B1 c.521T>C polymorphism, with the exception of simvastatin.

Candidate‐Gene Study of Functional Polymorphisms inSLCO1B1andCYP3A4/5and the Cholesterol‐Lowering Response to Simvastatin

“…Our study findings regarding SLCO1B1 521C were consistent with those observed in Heart Protection Study 15 and in the meta-analysis reported by Duo et al 14…”

“…[14]: SLCO1B1 521C was associated with a diminished cholesterol-lowering response. The consistencies regarding the magnitude and direction of this effect not only support the validity of our study but also provide addition evidence supporting the central role of SLCO1B1 in the pharmacology of simvastatin.…”

“…Fu et al 13 reported the percent reduction of LDL-C in a study of 174 patients of Chinese ancestry who received 20 mg simvastatin daily for 4 months was 27.2 ± 5.4, 28.9 ± 5.9, and 30.8 ± 5.4 for homozygous SLCO1B1 521C carriers, heterozygous SLCO1B1 521C carriers, and wildtype, respectively. As these reported findings were only suggestive trends, Dou et al 14 performed a meta-analysis of these studies and determined that the association between SLCO1B1 521C and cholesterol reductions was statistically significant. Hopewell et al 15 reported similar findings in the Heart Protection Study of 18,705 patients who received 40 mg simvastatin daily for 4-6 weeks: the percent reduction of LDL-C was 42.4 ± 0.2, 43.6 ± 0.4, and 44.7± 0.4 for homozygous SLCO1B1 521C carriers, heterozygous SLCO1B1 521C carriers, and wildtype, respectively.…”

“…As these reported findings were only suggestive trends, Dou et al . performed a meta-analysis of these studies and determined that the association between SLCO1B1 521C and cholesterol reductions was statistically significant [14]. Hopewell et al .…”

The Influences of SLCO1B1 and ABCB1 Genotypes on the Pharmacokinetics of Simvastatin, in Relation to CYP3A4 Inhibition

“…We estimate that patients with both risk factors are likely to have a much higher chance of developing myopathy. In addition, it is worth noting that both the FDA and the UK Medicines and Healthcare products Regulatory Agency propose a 50% lower dose of simvastatin for patients who coadminister amlodipine -it is unknown how this practice will influence the clinical outcomes of simvastatin treatment, particularly in patients carrying the SLCO1B1 c.521T>C variant, who are less responsive to simvastatin [33,34]. In conclusion, SLCO1B1 geno typing may be critical for simvastatin users who unavoidably take CYP3A4 inhibitors such as amlodipine, in order to lower the risk of adverse effects and impaired drug efficacy.…”