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

January 20, 2010

J Am Coll Cardiol. 2009 Oct 20;54(17):1609-16

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

Voora D, Shah SH, Spasojevic I, Ali S, CR, Salisbury BA, Ginsburg GS.

Division of Cardiovascular Medicine, Duke University Medical Center, Durham,

North Carolina 27708, USA.

Comment in:

J Am Coll Cardiol. 2009 Oct 20;54(17):1617-8.

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.

Recommended Posts