A systematic review and meta-analysis of genotype-based and individualized data analysis of SLCO1B1 gene and statin-induced myopathy

Abstract

This meta-analysis was conducted to determine the genotypic effects of rs4149056 and rs2306283 polymorphism in SLCO1B1 gene on myopathy in patients with statin. Studies were searched using multiple databases and selected following inclusion criteria. Two reviewers independently performed data extraction and assessments for risk of bias. Fixed-or-random-effect was applied to pool allele frequency/effects. Mixed-effect logit model was used to pool genotypic effects using individual patient data. Heterogeneity and publication bias were explored. Fourteen studies were pooled for rs4149056; the minor C allele frequency were 15% in Caucasians and 14% in Asians. Six studies were pooled for rs2306283; the minor G allele frequency was 34% in Caucasian and 75% in Asians. Genotypic effects of rs4149056 polymorphism in Caucasians indicated that statin users who carried CC and TC genotypes had a significantly higher risk of myopathy than those who carried TT genotype, with a pooled odds ratio (OR) of 2.9 (95% confidence interval, 1.59, 5.34) and 1.6 (1.20, 2.16), respectively. For subgroup analysis, CC and TC genotypes also suggested a higher risk of myopathy in simvastatin users [OR = 2.8 (1.17, 6.77) and OR = 1.8 (1.15, 2.77), respectively] and in atorvastatin users [OR = 4.0 (1.23, 12.63) and OR = 2.0 (1.11, 3.52), respectively] than those who carried TT genotype. There was no significant association between rs2306283 polymorphism and myopathy in Caucasians and Asians. There was no evidence of publication bias for both polymorphisms.

Effect of Genetic Variations in Drug-Metabolizing Enzymes and Drug Transporters on the Pharmacokinetics of Rifamycins: A Systematic Review

“…Similarly, no myopathy was observed with rs2306283 polymorphism which was observed in other SLCO1B1 genes in patients taking statins suggesting no effect or increased activity of the mutant variant. 57 …”

A Cost–Consequence Analysis of Preemptive SLCO1B1 Testing for Statin Myopathy Risk Compared to Usual Care

“…Other important considerations that may impact the utility of SLCO1B1 testing are recent changes in prescribing patterns and medication selection, such as the general transition away from simvastatin to atorvastatin as a first-option treatment [79,80]. On the other hand, this may eventually lead to additional reliance on SLCO1B1 testing as a tool to help ameliorate SAMS-related events given mounting evidence of the relationships between SLCO1B1 and both atorvastatin-related [10] and lovastatin-related [11] myotoxicity. However, due to the relative infrequency of SAMS, its multicausal nature, and the costs and outcomes observed here, standalone SLCO1B1 testing may only be appropriate as a single test for patients predisposed to SAMS due to other risk factors or in a reactive manner for those who respond poorly to statin initiation [81,82].…”

“…Further, given current CPIC recommendations, we only modeled simvastatinrelated outcomes within our hypothetical cohort. Estimates here may be conservative with respect to the potential effects of SLCO1B1 testing in light of mounting evidence for atorvastatin-and lovastatin-induced myotoxicity [10,11]. Future research assessing the costs and consequences of SLCO1B1 testing may benefit from incorporating costs beyond those realized solely by the health system, as well as assessing costs and consequences across a range of statin medications, health care settings, and extended time horizons.…”

“…Of the growing list of actionable drug-gene associations, one of the most wellvalidated is the interaction between solute carrier organic anion transporter family member 1B1 (SLCO1B1) and statin-associated muscle symptoms (SAMS) [6][7][8]. The evidence for this relationship is strongest for simvastatin but may be variably present for other types of statin medications and within specific ancestries with minor C risk alleles present in up to 20% of some populations [8][9][10][11]. Of carriers, greater than 60% of statin myopathy cases may be attributable to the C variant [6].…”

Statins Neuromuscular Adverse Effects

“…rs4149056 is a non-synonymous missense variant in exon 5 of the SLCO1B1 gene, altering a valine amin oacid with alanine at position 174. This variant has a strong association with simvastatin, and for this reason, patients with rs4149056, taking this kind of statin, should assume a lower dose of simvastatin or other statins with a narrow monitoring of creatine kinase (CK levels) [ 31 , 32 ].…”