Genotype-Guided Statin Therapy

Seip, Richard L.; Duconge, Jorge; Ruaño, Gualberto

doi:10.1007/978-1-60761-283-4_10

Cited by 2 publications

(2 citation statements)

References 117 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Markers predictive of statin induced low density lipoprotein cholesterol lowering have been identified by many groups (25). Validation of markers for statin safety and efficacy is essential for development of the tools to bring genetically personalized medicine into the mainstream of cardiovascular management(26).…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of statin-induced myalgia assessed by physiogenomic associations

Ruaño¹,

Windemuth²,

Wu³

et al. 2011

Atherosclerosis

Self Cite

View full text Add to dashboard Cite

Objective We investigated genetic variants predictive of muscular side effects in patients treated with statins. We utilized a physiogenomic approach to prototype a multi-gene panel correlated with statin-induced myalgia. Background Statin induced myalgia occurs in ∼10% of lipid clinic outpatients. Its clinical manifestation may depend in part upon gene variation from patient to patient. Methods We genotyped 793 patients (377 with myalgia and 416 without) undergoing statin therapy at four U.S. outpatient clinic sites to evaluate 31 candidate genes from the literature for their association with statin-induced common myalgia. Results Three previously hypothesized candidate genes were validated: COQ2 (rs4693570) encoding para-hydroxybenzoate-polyprenyltransferase, which participates in the biosynthesis of coenzyme Q10 (p<0.000041); ATP2B1 (rs17381194) which encodes a calcium transporting ATPase involved in calcium homeostasis (p<0.00079); and DMPK (rs672348) which encodes a protein kinase implicated in myotonic dystrophy (p<0.0016). Conclusions The candidate genes COQ2, ATP2B1, and DMPK, representing pathways involved in myocellular energy transfer, calcium homeostasis, and myotonic dystonia, respectively, were validated as markers for the common myalgia observed in patients receiving statin therapy. The three genes integrated into a physiogenomic predictive system could be relevant to myalgia diagnosis and prognosis in clinical practice.

show abstract

Section: Discussionmentioning

confidence: 99%

Mechanisms of statin-induced myalgia assessed by physiogenomic associations

Ruaño¹,

Windemuth²,

Wu³

et al. 2011

Atherosclerosis

Self Cite

View full text Add to dashboard Cite

show abstract

“…The elevation of CK activity to 10-fold ULN (upper limit of normal) indicates severe statin-induced neuromyopathy [45]. Pharmacokinetic gene-focused hypotheses have their basis on the increased plasma statin concentrations resulting from decreased first pass hepatic clearance (variation in drug transporters) and metabolism (variation in cytochrome p450 and glucuronidation pathways) [46]. …”

Section: Statin Safetymentioning

confidence: 99%