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The SLCO1B1*5Genetic Variant Is Associated With Statin-Induced Side Effects
Open accessAbstract
Objectives Identify SNPs associated with mild statin-induced side effects. Background Statin-induced side effects can interfere with therapy. SNPs in cytochrome P450 enzymes impair statin metabolism; the reduced function SLCO1B1*5 allele impairs statin clearance and is associated with simvastatin-induced myopathy with CK elevation. Methods The STRENGTH study was a pharmacogenetics study of statin efficacy and safety. Subjects (n=509) were randomized to atorvastatin 10mg, simvastatin 20mg, or pravastatin 10mg followed by 80mg, 80mg, and 40mg, respectively. We defined a composite adverse event (CAE) as discontinuation for any side effect, myalgia, or CK>3× baseline during follow-up. We sequenced CYP2D6, CYP2C8, CYP2C9, CYP3A4, and SLCO1B1 and tested seven reduced function alleles for association with the CAE. Results The CAE occurred in 99 subjects (54 discontinuations, 49 myalgias, and nine 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 ≥ 1 allele in CAE vs. no CAE groups, 37% vs. 25%, p=0.03) and those with CAE with no significant CK elevation (p≤ 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 highest 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 > 3 times normal to milder, statin-induced, muscle side effects.
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Self-citationWilke, R. A., Ramsey, L. B., Johnson, S. G., Maxwell, W. D., McLeod, H. L., Voora, D., Krauss, R. M., Roden, D. M., Feng, Q., Cooper-DeHoff, R. M., et al. (2012) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2012.57 · Cited by 332
Self-citationPhenotype standardization for statin-induced myotoxicity
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Metadata
- Authors
- Voora, D., Shah, S. H., Spasojevic, I., Ali, S., Reed, C. R., Salisbury, B. A., & Ginsburg, G. S.
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2009-10
- Volume
- 54
- Issue
- 17
- Pages
- 1609-1616
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W2139681313
- Cited by
- 502
- References
- 29
- FWCI
- 38.02
- Type
- journal article
- Language
- en
- Open access
- bronze
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