Statin use is associated with a variety of overtly related muscle symptoms 
including muscle pain, myalgia, creatine kinase elevations without pain with 
myolysis and myositis (rhabdomyolysis), a potentially fatal side effect that led 
to the withdrawal of cerivastatin in 2001. Unintended drug response phenotypes 
have an impact on patient compliance and sometimes patient health and the 
assessment of risk on an individual basis could enhance therapeutic benefit. We 
therefore investigated whether common single nucleotide polymorphisms were 
associated with the expression of broadly grouped atorvastatin-induced muscle 
events in a case-control study (n=263 samples, n=388 SNPs). Of a number of 
associations identified in a discovery sample (51 atorvastatin-induced muscle 
and 55 normal) only those corresponding to the CYP2D6*4 allele were 
significantly associated in the sample (24 atorvastatin-induced muscle and 133 
normal) (Discovery P=0.004, odds ratio=3.6; Validation P=0.036, odds ratio=2.7; 
total P=0.001, odds ratio=2.5). The frequency of the CYP2D6*4 allele was about 
50% in atorvastatin-induced muscle patients but only 28% in controls, similar to 
that of other patient types (28.5%). The association was independent of various 
demographic variables and not explained by gross demographic, clinical or 
population-structure differences among cases and controls. Surprisingly, the 
CYP2D6*4 allele appeared similarly distributed among controls and patients 
expressing simvastatin-induced muscle events (n=169, frequency in case 
participants=49.2%, P=0.067, odds ratio=1.7). Our results suggest that the 
CYP2D6*4 allele is associated with broadly related muscle events caused by at 
least two structurally dissimilar HMG-CoA reductase inhibitors, and as such, may 
have implications for a better understanding of this statin-wide phenomena.