SLCO1B1*5 genetic variant assoc with statin adverse effects

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SLCO1B1*5 genetic variant assoc with statin adverse effects

Voora D, Shah SH, Spasojevic I, et al. The SLCO1B1*5 genetic variant is associated with statin-induced side effects. J Am Coll Cardiol 2009 Oct 20;54(17):1609-1616.


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J Am Coll Cardiol, 2009; 54:1609-1616, doi:10.1016/j.jacc.2009.04.053
© 2009 by the American College of Cardiology Foundation

The SLCO1B1*5 Genetic Variant Is Associated With Statin-Induced Side Effects

Deepak Voora, MD*,, Svati H. Shah, MD, MHS*,,, Ivan Spasojevic, PhD, Shazia Ali, PharmD, Carol R. Reed, MD¶, Benjamin A. Salisbury, PhD¶ and Geoffrey S. Ginsburg, MD, PhD*,,,*
* Division of Cardiovascular Medicine, Duke University Medical Center, Durham, North Carolina
Center for Human Genetics, Duke University Medical Center, Durham, North Carolina
Department of Medicine, Duke University Medical Center, Durham, North Carolina
Institute for Genome Sciences & Policy, Duke University Medical Center, Durham, North Carolina
¶ PGxHealth, LLC, New Haven, Connecticut
Manuscript received January 13, 2009; revised manuscript received April 9, 2009, accepted April 13, 2009.
* Reprint requests and correspondence: Dr. Geoffrey S. Ginsburg, Institute for Genome Sciences & Policy, Center for Genomic Medicine, 2117 CIEMAS, 101 Science Drive, Duke University, DUMC Box 3382, Durham, North Carolina 27708 (Email:


Objectives: We sought to identify single nucleotide polymorphisms associated with mild statin-induced side effects.
Background: Statin-induced side effects can interfere with therapy. Single nucleotide polymorphisms in cytochrome P450 enzymes impair statin metabolism; the reduced function SLCO1B1*5 allele impairs statin clearance and is associated with simvastatin-induced myopathy with creatine kinase (CK) elevation.
Methods: The STRENGTH (Statin Response Examined by Genetic Haplotype Markers) study was a pharmacogenetics study of statin efficacy and safety. Subjects (n = 509) were randomized to atorvastatin 10 mg, simvastatin 20 mg, or pravastatin 10 mg followed by 80 mg, 80 mg, and 40 mg, respectively. We defined a composite adverse event (CAE) as discontinuation for any side effect, myalgia, or CK >3x upper limit of normal during follow-up. We sequenced CYP2D6, CYP2C8, CYP2C9, CYP3A4, and SLCO1B1 and tested 7 reduced function alleles for association with the CAE.
Results: The CAE occurred in 99 subjects (54 discontinuations, 49 myalgias, and 9 CK elevations). Sex was associated with CAE (percent female in CAE vs. no CAE groups, 66% vs. 50%, p Conclusions: SLCO1B1*5 genotype and female sex were associated mild statin-induced side effects. These findings expand the results of a recent genome-wide association study of statin myopathy with CK >3x normal to milder, statin-induced, muscle side effects.

Key Words: hydroxymethylglutaryl-CoA reductase inhibitors • pharmacogenetics • single nucleotide polymorphisms • adverse events • clinical trial • myopathy

Abbreviations and Acronyms
  AE = adverse event
  CAE = composite adverse event
  CK = creatine kinase
  FDR = false discovery rate
  LDL = low-density lipoprotein
  MAF = minor allele frequencies
  SNP = single nucleotide polymorphism