The SLCO1B1*5 genetic variant is associated with statin-induced side effects.

Published

Journal Article

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 < 0.01). SLCO1B1*5 was associated with CAE (percent with > or = 1 allele in CAE vs. no CAE groups, 37% vs. 25%, p = 0.03) and those with CAE with no significant CK elevation (p < or = 0.03). Furthermore, there was evidence for a gene-dose effect (percent with CAE in those with 0, 1, or 2 alleles: 19%, 27%, and 50%, trend p = 0.01). Finally, the CAE risk appeared to be greatest in those carriers assigned to simvastatin. 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.

Full Text

Duke Authors

Cited Authors

  • Voora, D; Shah, SH; Spasojevic, I; Ali, S; Reed, CR; Salisbury, BA; Ginsburg, GS

Published Date

  • October 20, 2009

Published In

Volume / Issue

  • 54 / 17

Start / End Page

  • 1609 - 1616

PubMed ID

  • 19833260

Pubmed Central ID

  • 19833260

Electronic International Standard Serial Number (EISSN)

  • 1558-3597

Digital Object Identifier (DOI)

  • 10.1016/j.jacc.2009.04.053

Language

  • eng

Conference Location

  • United States