Physiogenomic association of statin‐related myalgia to serotonin receptors

Ruaño, Gualberto; Thompson, Paul D.; Windemuth, Andreas; Seip, Richard L.; Dande, Amit S.; Sorokin, Alexey V.; Kocherla, Mohan; Smith, Andrew P.; Holford, Theodore R.; Wu, Alan H.B.

doi:10.1002/mus.20871

Cited by 66 publications

(43 citation statements)

References 53 publications

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“…SNPs in the HTR3B and HTR7 genes, rs2276307 and rs1935349, were significantly associated with myalgia score (p = 0.007 and p = 0.026, respectively); however, there was no significant association with CK (log) levels [38].…”

Section: Coq10mentioning

confidence: 87%

Genetic Determinants of Statin-Associated Myopathy

Molokhia

Bhatia

Nitsch

2008

Personalized Medicine

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Lipid-lowering drugs, especially 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins), are widely used in the treatment of patients with increased risk of cardiovascular disease, with well-documented benefits. However, in rare cases, lipid-lowering drugs may cause myopathy or rhabdomyolysis, the risk of which is increased by certain drug-drug interactions. Polymorphisms of metabolizing pathways, including CYP, and efflux transporters, such as MDR1 and SLCO1B1, may cause intersubject variability in plasma statin levels and therefore may be responsible for susceptibility to myopathy. The aim of this review is to summarize selected genetic polymorphisms that predispose to statin-related myopathy (including combined studies of myopathy and myalgia). Genome-wide studies suggest that there is a strong candidate variant within the SLCO1B1 gene (rs4149056) for statin-associated myopathy in a UK (European) population. An enhanced understanding of statin-related myopathy may lead to safer drug development and use.

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Section: Coq10mentioning

confidence: 87%

Genetic Determinants of Statin-Associated Myopathy

Molokhia

Bhatia

Nitsch

2008

Personalized Medicine

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“…Genetic factors may also influence the likelihood of developing myalgia. In a study of 5HT-receptor (HRT) gene families in statin-treated patients, a significant association between the occurrence of myalgia and polymorphisms in HRT3B and HTR7 was seen [35].…”

Section: Genetic Susceptibilitymentioning

confidence: 99%

Update on Toxic Myopathies

Mastaglia

Needham

2011

Curr Neurol Neurosci Rep

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The toxic myopathies are a clinically and pathologically diverse group of disorders that can be caused by a variety of therapeutic agents used in clinical practice, as well as various venoms and other biological toxins. The most important iatrogenic causes are the statin and fibrate cholesterol-lowering agents that can cause a severe necrotizing myopathy and acute rhabdomyolysis and myoglobinuria. The current update focuses on the mechanisms of statin myotoxicity and the importance of genetic predisposing factors for statin myopathy, as well as the recently described form of necrotizing autoimmune myopathy, which is associated with antibodies to the 3-hydroxy-3-methylglutaryl-coenzyme A reductase enzyme and is responsive to aggressive immunotherapy. Mitochondrial myopathies associated with antiretroviral agents and the pyrimidine nucleoside analogue clevudine, and recent reports of myopathies caused by ingestion of red yeast rice and toxic species of mushrooms are also discussed.

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“…Inherited increased susceptibility to the perception of pain, related to genetic variation in serotonergic receptors, can increase the incidence of statin myopathy, and this may be partially relevant to patients with a pre-existing history of chronic generalized pain [37].…”

Section: Risk Factorsmentioning

confidence: 99%