Statin-Associated Myopathy: From Genetic Predisposition to Clinical Management

Vráblík, Michal; Zlatohlávek, L.; Štulc, Tomáš; Adámková, Věra; Prusíková, Martina; Schwarzová, Lucie; Hubáček, J.; Češka, R.

doi:10.33549/physiolres.932865

Cited by 50 publications

(23 citation statements)

References 42 publications

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“…Human COQ10A and COQ10B are co-orthologs of yeast COQ10 located on human chromosome 12 and chromosome 2, respectively (55). The polymorphisms in COQ10A (P79H, P231S) and COQ10B (L48F) are thought to be one of the genetic factors predisposing patients to statinassociated myopathy (56,57). The underlying molecular mechanisms of statin-associated myopathy are proposed to be isoprenoid depletion, inhibition of CoQ biosynthesis, disruption of cholesterol homeostasis, or disturbance of calcium metabolism (58).…”

Section: Expression Of Either Coq10a or Coq10b From Humans Restores Respiratory Growth Of The Yeast Coq10 Mutantmentioning

confidence: 99%

Human COQ10A and COQ10B are distinct lipid-binding START domain proteins required for coenzyme Q function

Tsui

Pham

Amer

et al. 2019

Journal of Lipid Research

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Coenzyme Q (ubiquinone or Q) functions as an essential redox‐active lipid in respiratory electron and proton transport in cellular energy metabolism, and it is an important lipid‐soluble antioxidant in cellular membranes. In Saccharomyces cerevisiae, proteins Coq3‐Coq9, as well as Coq11, assemble into a multi‐subunit protein complex called the CoQ‐synthome, which is required for Q biosynthesis. Coq10, a putative steroidogenic acute regulatory (StAR)‐related lipid transfer (StART) domain protein is not a member of the CoQ‐synthome, but is required for the proper assembly of the CoQ‐synthome, efficient de novo Q biosynthesis during early‐log phase, and the function of Q in respiration and as an antioxidant. Humans possess two isoforms, namely COQ10A and COQ10B. Based on the RNA‐seq data from NCBI, COQ10A is predominantly expressed in heart while COQ10B is present in all tissues, suggesting that COQ10B is probably serving a more general role. Previous studies have shown rescue of S. cerevisiae coq10Δ respiration deficient phenotype by expression of human COQ10A. Here we present new evidence showing rescue of S. cerevisiae coq10Δ by expression of either the human COQ10A or COQ10B homolog, as determined by restoration of respiratory growth on non‐fermentable carbon sources, de novo Q biosynthesis, as well as restoration of the CoQ‐synthome. Support or Funding Information This research was supported by NSF MCB‐1330803 and Ruth L. Kirschstein National Research Service Award GM007185. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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Section: Expression Of Either Coq10a or Coq10b From Humans Restores Respiratory Growth Of The Yeast Coq10 Mutantmentioning

confidence: 99%

Human COQ10A and COQ10B are distinct lipid-binding START domain proteins required for coenzyme Q function

Tsui

Pham

Amer

et al. 2019

Journal of Lipid Research

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“…Contrary to randomized clinical trials, where the occurrence of adverse reactions ranges between 1 and 5%, actual clinical experience, as reported in the literature, suggests that the number of undesirable effects stemming from statin use is much higher (15-20%). 20 Statins are highly effective in dyslipidemia as monotherapy and are the main pillar of management in patients with dyslipidemia 21 .…”

Section: Discussionmentioning

confidence: 99%

Frequency of Statin-Induced Myopathy in Patients with Dyslipidemia Presenting in a Tertiary Care Hospital of Lahore

Asif¹,

Chachar²,

Haider³

et al. 2021

PJMHS

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Background: Frequency of dyslipidemia is on continuous rise in the developing countries including Pakistan. Many studies have shown that a raised LDL-cholesterol level, non-HDL cholesterol levels and decreased HDL-cholesterol levels are related with anraised risk of cardiovascular diseases and also certain muscle related symptoms. Aim: To find the frequency of statin-induced myopathy in dyslipidemic patients presenting in a tertiary care hospital. Methods It was a cross sectional study conducted among dyslipidemic patients presented at department of medicine and endocrinology, Unit-I Fatima Memorial hospital, Lahore. Non-probability consecutive sampling technique was used to select 230 dyslipidemic patients who met the inclusion criteria. Information was recorded on predesigned questionnaire regarding statin induced myopathy and socio-demographic variables. Results: In this study, the mean age statin induced myopathy respondents was 49.9±8.6 years while it was 49.9±9.4 years among not having statin induced myopathy.Statin induced myopathy was seen in 55 (23.9%) respondents while in 175 (76.1%) there was no statin induced myopathy. Gender among peripheral neuropathy showed that males were 42 and females were 13 in number; and among non-statin induced myopathy group there were 121 males and 54 females. Most of the middle income respondents were suffering from statin induced myopathy as compared to other income groups. Conclusion: This study reports an increased prevalence of statin induced myopathy among dyslipidemic patients. Male respondents were more in number than females but both had shown insignificant relationship with statin induced myopathy. The age>45 years of the respondents showed significant statistical difference with gender. Keywords: Statin Induced Myopathy, Dyslipidemia, Lahore

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“…SAMS has a highly variable clinical presentation ranging from a myopathic pattern, characterized by muscle tenderness, cramping and muscle aches, weakness and increased CK level (even 10 times higher the upper normal limit), to rhabdomyolysis [ 20 ]. Myopathy usually appears in patients who receive high doses of statins, especially when taking simvastatin 80 mg daily, which lead to higher plasma levels of active statins metabolites, especially in the first year of treatment or after having increased the dosage.…”

Section: Statins and Skeletal Muscle Adverse Effectsmentioning

confidence: 99%

“…In the mitochondrial metabolism, Coenzyme Q10 (CoQ10), also known as ubiquinone, is one of the end products of the mevalonate pathway. Statins use lead to its depletion in a dose-dependent manner and it could be associated with an elevated risk of myopathy [ 20 ].…”

Section: Pathogenesis Of Samsmentioning

confidence: 99%

Statins Neuromuscular Adverse Effects

Attardo

Musumeci

Velardo

et al. 2022

IJMS

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Statins are drugs widely prescribed in high-risk patients for cerebrovascular or cardiovascular diseases and are, usually, safe and well tolerated. However, these drugs sometimes may cause neuromuscular side effects that represent about two-third of all adverse events. Muscle-related adverse events include cramps, myalgia, weakness, immune-mediated necrotizing myopathy and, more rarely, rhabdomyolysis. Moreover, they may lead to peripheral neuropathy and induce or unmask a preexisting neuromuscular junction dysfunction. A clinical follow up of patients assuming statins could reveal early side effects that may cause neuromuscular damage and suggest how to better modulate their use. In fact, statin dechallenge or cessation, or the alternative use of other lipid-lowering agents, can avoid adverse events. This review summarizes the current knowledge on statin-associated neuromuscular adverse effects, diagnosis, and management. It is conceivable that the incidence of neuromuscular complications will increase because, nowadays, use of statins is even more diffused than in the past. On this purpose, it is expected that pharmacogenomic and environmental studies will help to timely predict neuromuscular complications due to statin exposure, leading to a more personalized therapeutic approach.

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Statin-Associated Myopathy: From Genetic Predisposition to Clinical Management

Cited by 50 publications

References 42 publications

Human COQ10A and COQ10B are distinct lipid-binding START domain proteins required for coenzyme Q function

Human COQ10A and COQ10B are distinct lipid-binding START domain proteins required for coenzyme Q function

Frequency of Statin-Induced Myopathy in Patients with Dyslipidemia Presenting in a Tertiary Care Hospital of Lahore

Statins Neuromuscular Adverse Effects

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