Genetic Influence in Statin Intolerance

Puccetti, Luca; Scarpini, Francesca; Cappellone, Roberta; Auteri, Alberto

doi:10.1038/clpt.2011.114

Cited by 2 publications

(3 citation statements)

References 6 publications

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“…Our finding is also consistent with a recent meta‐analysis of 14 studies comprising 3,265 myopathy patients and 7,743 controls . Additionally, previously reported associations in the GATM , COQ2 , and human eyes shut ortholog gene loci were not replicated.…”

Section: Discussionsupporting

confidence: 92%

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Genomewide Association Study of Statin‐Induced Myopathy in Patients Recruited Using the UK Clinical Practice Research Datalink

Carr

Francis

Jorgensen

et al. 2019

Clin Pharma and Therapeutics

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Statins can be associated with myopathy. We have undertaken a genomewide association study (GWAS) to discover and validate genetic risk factors for statin-induced myopathy in a "real-world" setting. One hundred thirtyfive patients with statin myopathy recruited via the UK Clinical Practice Research Datalink were genotyped using the Illumina OmniExpress Exome version 1.0 Bead Chip and compared with the Wellcome Trust Case-Control Consortium (n = 2,501). Nominally statistically significant single nucleotide polymorphism (SNP) signals in the GWAS (P < 5 × 10 −5 ) were further evaluated in several independent cohorts (comprising 332 cases and 449 drug-tolerant controls). Only one (rs4149056/c.521C>T in the SLCO1B1 gene) SNP was genomewide significant in the severe myopathy (creatine kinase > 10 × upper limit of normal or rhabdomyolysis) group (P = 2.55 × 10 −9 ; odds ratio 5.15; 95% confidence interval 3.13-8.45). The association with SLCO1B1 was present for several statins and replicated in the independent validation cohorts. The data highlight the role of SLCO1B1 c.521C>T SNP as a replicable genetic risk factor for statin myopathy. No other novel genetic risk factors with a similar effect size were identified.The 3-hydroxy-3-methyl-glutaryl-coenzyme A inhibitors, or statins, are a widely prescribed class of drugs for the treatment of hyperlipidemia. Although generally well tolerated, a small proportion of patients can develop muscle-related adverse effects. 1 These can range from mild muscle pain without creatine kinase (CK) elevation, where causality can be difficult to assess,

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Section: Discussionsupporting

confidence: 92%

“…Other genetic markers have been associated with statin‐myopathy, including polymorphisms in the coenzyme Q2 4‐hydroxybenzoate polyprenyltransferase ( COQ2 ) and human eyes shut ortholog genes, but have not been independently replicated. The genetic association of statin myopathy with the GATM gene has also not been replicated …”

mentioning

confidence: 99%

Genomewide Association Study of Statin‐Induced Myopathy in Patients Recruited Using the UK Clinical Practice Research Datalink

Carr

Francis

Jorgensen

et al. 2019

Clin Pharma and Therapeutics

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“…Recent studies 9 , 15 have shown that variation in the COQ2 gene also predisposes an individual to statin-induced myopathy. However, we could not replicate the association with the COQ2 rs4693075 polymorphism in our patient group.…”

Section: Discussionmentioning

confidence: 99%

SLCO1B1 Genetic Variant Associated With Statin-Induced Myopathy: A Proof-of-Concept Study Using the Clinical Practice Research Datalink

Carr¹,

O'Meara²,

Jorgensen

et al. 2013

Clin Pharmacol Ther

127

132

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This study aimed to determine whether patients with statin-induced myopathy could be identified using the United Kingdom Clinical Practice Research Datalink, whether DNA could be obtained, and whether previously reported associations of statin myopathy with the SLCO1B1 c.521T>C and COQ2 rs4693075 polymorphisms could be replicated. Seventy-seven statin-induced myopathy patients (serum creatine phosphokinase (CPK) > 4× upper limit of normal (ULN)) and 372 statin-tolerant controls were identified and recruited. Multiple logistic regression analysis showed the SLCO1B1 c.521T>C single-nucleotide polymorphism to be a significant risk factor (P = 0.009), with an odds ratio (OR) per variant allele of 2.06 (1.32–3.15) for all myopathy and 4.09 (2.06–8.16) for severe myopathy (CPK > 10× ULN, and/or rhabdomyolysis; n = 23). COQ2 rs4693075 was not associated with myopathy. Meta-analysis showed an association between c.521C>T and simvastatin-induced myopathy, although power for other statins was limited. Our data replicate the association of SLCO1B1 variants with statin-induced myopathy. Furthermore, we demonstrate how electronic medical records provide a time- and cost-efficient means of recruiting patients with severe adverse drug reactions for pharmacogenetic studies.

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Genetic Influence in Statin Intolerance

Cited by 2 publications

References 6 publications

Genomewide Association Study of Statin‐Induced Myopathy in Patients Recruited Using the UK Clinical Practice Research Datalink

Genomewide Association Study of Statin‐Induced Myopathy in Patients Recruited Using the UK Clinical Practice Research Datalink

SLCO1B1 Genetic Variant Associated With Statin-Induced Myopathy: A Proof-of-Concept Study Using the Clinical Practice Research Datalink

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