Differential effect of the rs4149056 variant in SLCO1B1 on myopathy associated with simvastatin and atorvastatin.
Statins reduce cardiovascular morbidity and mortality in appropriately selected patients. However, statin-associated myopathy is a significant risk associated with these agents. Recently, variation in the SLCO1B1 gene was reported to predict simvastatin-associated myopathy. The aim of this study was to replicate association of the rs4149056 variant in SLCO1B1 with severe statin-associated myopathy in a cohort of patients using a variety of statin medications and to investigate the association with specific statin types. We identified 25 cases of severe statin-associated myopathy and 84 controls matched for age, gender, statin type and dose. The rs4149056 variant in SLCO1B1 was not significantly associated with myopathy in this group as a whole. However, when subjects were stratified by statin type, the SLCO1B1 rs4149056 genotype was significantly associated with myopathy in patients who received simvastatin, but not in patients who received atorvastatin. Our findings provide further support for a role for SLCO1B1 genotype in simvastatin-associated myopathy, and suggest that this association may be stronger for simvastatin compared with atorvastatin.
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
L R
LR
Brunham
P J
PJ
Lansberg
L
L
Zhang
F
F
Miao
C
C
Carter
G K
GK
Hovingh
H
H
Visscher
J W
JW
Jukema
A F
AF
Stalenhoef
C J D
CJ
Ross
B C
BC
Carleton
J J P
JJ
Kastelein
M R
MR
Hayden
D000328:Adult; D000368:Aged; D000069059:Atorvastatin; D001955:British Columbia; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006538:Heptanoic Acids / Q000009:adverse effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D008875:Middle Aged; D009135:Muscular Diseases / Q000139:chemically induced* / Q000235:genetics*; D009426:Netherlands; D016017:Odds Ratio; D027361:Organic Anion Transporters / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011758:Pyrroles / Q000009:adverse effects*; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D019821:Simvastatin / Q000009:adverse effects*
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D011758:Pyrroles; C503999:SLCO1B1 protein, human; D000069059:Atorvastatin; D019821:Simvastatin