Correlation between single-nucleotide polymorphisms and statin-induced myopathy: a mixed-effects model meta-analysis
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PHARMACOKINETICS AND DISPOSITION
Correlation between single-nucleotide polymorphisms and statin-induced myopathy: a mixed-effects model meta-analysis Qian Xiang 1 & Xiao-Dan Zhang 1 & Guang-Yan Mu 1 & Zhe Wang 1 & Zhi-Yan Liu 1 & Qiu-Fen Xie 1 & Kun Hu 1 & Zhuo Zhang 1 & Ling-Yue Ma 1 & Jie Jiang 2 & Yi-Min Cui 1,3 Received: 9 May 2020 / Accepted: 21 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Purpose A meta-analysis was performed to evaluate the correlation between single-nucleotide polymorphisms (SNPs) and risk of statin-induced myopathy (SIM). Methods We retrieved the studies published on SIM until April 2019 from the PubMed, Embase, and Cochrane Library databases. We collected data from 32 studies that analyzed 10 SNPs in five genes and included 21,692 individuals and nine statins. Results The analysis of the heterozygous (p = 0.017), homozygous (p = 0.002), dominant (p = 0.005), and recessive models (p = 0.009) of SLCO1B1 rs4149056 showed that this SNP increases the risk of SIM. Conversely, heterozygous (p = 0.048) and dominant models (p = 0.030) of SLCO1B1 rs4363657 demonstrated that this SNP is associated with a reduced risk of SIM. Moreover, an increased risk of SIM was predicted for carriers of the rs4149056 C allele among simvastatin-treated patients, whereas carriers of the GATM rs9806699 A allele among rosuvastatin-treated patients had a lower risk of SIM. Conclusion The meta-analysis revealed that the rs4149056 and rs4363657 SNPs in SLCO1B1 and the rs9806699 SNP in GATM are correlated with the risk of SIM. Keywords Meta-analysis . Single-nucleotide polymorphism . Mitochondrial myopathy . Hydroxymethylglutaryl-CoA reductase inhibitor
Introduction Statins act as inhibitors of the enzyme 3-hydroxy-3methylglutaryl-coenzyme A (HMG-CoA) reductase, thereby competitively inhibiting the synthesis of endogenous cholesterol. Although modern proprotein convertase subtilisin/kexin type 9 (PCSK9) serine protease inhibitors can also be used to Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/s00228-02003029-1. * Yi-Min Cui [email protected] 1
Department of Pharmacy, Peking University First Hospital, Beijing 100034, China
2
Department of Cardiology, Peking University First Hospital, Beijing 100034, China
3
Beijing, China
lower serum lipid levels, statins are still widely used in clinical treatment, since they are well-tolerated and improve the condition of patients with cardiovascular disease [1]. However, the prolonged use of statins may result in statin-induced myopathy (SIM), myalgia, and life-threatening rhabdomyolysis. The clinical manifestations of SIM include acute or chronic muscle pain, myasthenia, and elevated levels of creatine kinase (CK) in asymptomatic patients. The potential pathogenic mechanism underlying the emergence of SIM includes cholesterol deficiency, decreased stability and permeability of the myocyte membrane, coenzyme Q10 deficiency leading to dysfunctional mitochondrial respirat
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