SLCO1B1 521T &gt; C polymorphism associated with rosuvastatin-induced myotoxicity in Chinese coronary artery disease patients: a nested case–control study

Liu, Jue; Li, Xiaoying; Chen, Sheng; Zhang, Yan; Cai, Lijun; Yang, Min; Lai, Wen‐Ter; Ren, Bin; Zhong, Shilong

doi:10.1007/s00228-017-2318-z

Cited by 32 publications

(39 citation statements)

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“…The mutation allele frequency of SLCO1B1 388A>G was 74.99% (74.57% in male and 75.69% in female), and 521T>C was 11.50% (12.38% in male and 10.04% in female) in the Hakka population in our research. The results were similar to the study results of Liu et al, the allele frequency of SLCO1B1 388A>G was higher in Chinese Han than in Caucasians, while 521T>C was lower. The frequencies of haplotypes *1b/*1b (40.07%) and *1a/*1b (32.56%) of SLCO1B1 gene accounted for 72.63%, followed by *1b/*15 (14.40%), *1a/*1a (5.82%), *1a/*15 (5.57%), *15/*15 (1.45%), and *1a/*5 (0.12%).…”

Section: Discussionsupporting

confidence: 91%

Analysis of SLCO1B1 and APOE genetic polymorphisms in a large ethnic Hakka population in southern China

Zhong

et al. 2018

Clinical Laboratory Analysis

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Section: Discussionsupporting

confidence: 91%

Analysis of SLCO1B1 and APOE genetic polymorphisms in a large ethnic Hakka population in southern China

Zhong

et al. 2018

Clinical Laboratory Analysis

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“…Furthermore, a recent whole-exome sequencing endeavour reported that SLCO1B1 rs4149056 is associated with statin myopathy (mainly SVT or CVT cases), which reached multiple testing significance when limited to patients not on a fibrate; however, no novel rare coding signals were detected [111]. Intriguingly, SLCO1B1 rs4149056 has been recently associated with RVT myotoxicity (a composite of myalgias to rhabdomyolysis) in Han Chinese patients [109,176], although it was not previously associated with myalgias in patients of European descent receiving RVT [112]. A recent meta-analysis, largely including these studies, further suggested an association between rs4149056 and RVT myotoxicity [116].…”

Section: Slco1b1 Influx Transportermentioning

confidence: 99%

Statin-Related Myotoxicity: A Comprehensive Review of Pharmacokinetic, Pharmacogenomic and Muscle Components

Turner

Pirmohamed

2019

JCM

141

126

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Statins are a cornerstone in the pharmacological prevention of cardiovascular disease. Although generally well tolerated, a small subset of patients experience statin-related myotoxicity (SRM). SRM is heterogeneous in presentation; phenotypes include the relatively more common myalgias, infrequent myopathies, and rare rhabdomyolysis. Very rarely, statins induce an anti-HMGCR positive immune-mediated necrotizing myopathy. Diagnosing SRM in clinical practice can be challenging, particularly for mild SRM that is frequently due to alternative aetiologies and the nocebo effect. Nevertheless, SRM can directly harm patients and lead to statin discontinuation/non-adherence, which increases the risk of cardiovascular events. Several factors increase systemic statin exposure and predispose to SRM, including advanced age, concomitant medications, and the nonsynonymous variant, rs4149056, in SLCO1B1, which encodes the hepatic sinusoidal transporter, OATP1B1. Increased exposure of skeletal muscle to statins increases the risk of mitochondrial dysfunction, calcium signalling disruption, reduced prenylation, atrogin-1 mediated atrophy and pro-apoptotic signalling. Rare variants in several metabolic myopathy genes including CACNA1S, CPT2, LPIN1, PYGM and RYR1 increase myopathy/rhabdomyolysis risk following statin exposure. The immune system is implicated in both conventional statin intolerance/myotoxicity via LILRB5 rs12975366, and a strong association exists between HLA-DRB1*11:01 and anti-HMGCR positive myopathy. Epigenetic factors (miR-499-5p, miR-145) have also been implicated in statin myotoxicity. SRM remains a challenge to the safe and effective use of statins, although consensus strategies to manage SRM have been proposed. Further research is required, including stringent phenotyping of mild SRM through N-of-1 trials coupled to systems pharmacology omics- approaches to identify novel risk factors and provide mechanistic insight.

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“…However, the situation is more complex than that and sex and ethnicity are also relevant. Thus, the same SLCO1B1 polymorphism has recently been shown to be associated with increased myotoxicity in Chinese people receiving rosuvastatin 19. There is as yet no evidence to support the cost effectiveness of screening for this polymorphism or for those in other genes, before starting statins.…”

Section: Statin-related Myopathiesmentioning

confidence: 99%

Statin-related myopathies

Hilton‐Jones

2018

Pract Neurol

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Statins are the Marmite ('You either love it or hate it!') of the drug world, both in terms of therapeutic benefit and risk of side effects. Proponents think that they are potential life-savers, opponents that their main benefit is lining the pockets of pharma. Some consider side effects to be a major issue, outweighing any therapeutic benefit, others that they are rare and essentially innocuous. Statin-induced myalgia is relatively common but often mild and for most people does not limit treatment. In others, reducing the dose or changing the preparation may help. In all, withdrawal of the statin leads to resolution. Statin-induced rhabdomyolysis, most often precipitated by drug-drug interaction, affects only a tiny proportion of statin users, but because of the widespread prescribing of statins is an important clinical problem. Statin-induced immune-mediated necrotising myopathy represents a novel disease mechanism and clinically mimics forms of myositis. Resolution often requires immunosuppressant drug treatment, as well as statin withdrawal.

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SLCO1B1 521T > C polymorphism associated with rosuvastatin-induced myotoxicity in Chinese coronary artery disease patients: a nested case–control study

Abstract: SLCO1B1 (rs4149056, 521T > C) is associated with statin-induced myotoxicity in Chinese patients with coronary artery disease. In addition, SLCO1B1 521C mutant allele increased the risk of rosuvastatin-associated myotoxicity.

Cited by 32 publications

References 32 publications

Analysis of SLCO1B1 and APOE genetic polymorphisms in a large ethnic Hakka population in southern China

Analysis of SLCO1B1 and APOE genetic polymorphisms in a large ethnic Hakka population in southern China

Statin-Related Myotoxicity: A Comprehensive Review of Pharmacokinetic, Pharmacogenomic and Muscle Components

Statin-related myopathies

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