An association study of 43 SNPs in 16 candidate genes with atorvastatin response.
Variation in individual response to statin therapy has been widely studied for a potential genetic component. Multiple genes have been identified as potential modulators of statin response, but few study findings have replicated. To further examine these associations, 2735 individuals on statin therapy, half on atorvastatin and the other half divided among fluvastatin, lovastatin, pravastatin and simvastatin were genotyped for 43 SNPs in 16 genes that have been implicated in statin response. Associations with low-density lipoprotein cholesterol (LDL-C) lowering, total cholesterol lowering, HDL-C elevation and triglyceride lowering were examined. The only significant associations with LDL-C lowering were found with apoE2 in which carriers of the rare allele who took atorvastatin lowered their LDL-C by 3.5% more than those homozygous for the common allele and with rs2032582 (S893A in ABCB1) in which the two groups of homozygotes differed by 3% in LDL-C lowering. These genetic effects were smaller than those observed with the demographic variables of age and gender. The magnitude of all the differences found is sufficiently small that genetic data from these genes should not influence clinical decisions on statin administration.
Thompson
J F
JF
Discovery Pharmacogenomics, Pfizer Global Research and Development, Eastern Point Road, MS8118D-3069, Groton, CT 06340, USA. john.f.thompson@pfizer.com
Man
M
M
Johnson
K J
KJ
Wood
L S
LS
Lira
M E
ME
Lloyd
D B
DB
Banerjee
P
P
Milos
P M
PM
Myrand
S P
SP
Paulauskis
J
J
Milad
M A
MA
Sasiela
W J
WJ
D000368:Aged; D053329:Apolipoprotein E2; D001057:Apolipoproteins E / Q000235:genetics; D000069059:Atorvastatin; D008076:Cholesterol, HDL / Q000187:drug effects; D008078:Cholesterol, LDL / Q000187:drug effects; D005260:Female; D005787:Gene Frequency; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011758:Pyrroles / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood; D044465:White People / Q000235:genetics
D053329:Apolipoprotein E2; D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D014280:Triglycerides; D000069059:Atorvastatin; D006903:Hydroxymethylglutaryl CoA Reductases