Meta-analysis of genome-wide association studies of HDL cholesterol response to statins.
BACKGROUND: In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Inter-individual variation in HDL-C response to statins may be partially explained by genetic variation. METHODS AND RESULTS: We performed a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with p<1×10-4 from the 16 769 statin-treated participants in the first analysis stage were followed up in an independent group of 10 951 statin-treated individuals, providing a total sample size of 27 720 individuals. The only associations of genome-wide significance (p<5×10-8) were between minor alleles at the CETP locus and greater HDL-C response to statin treatment. CONCLUSIONS: Based on results from this study that included a relatively large sample size, we suggest that CETP may be the only detectable locus with common genetic variants that influence HDL-C response to statins substantially in individuals of European descent. Although CETP is known to be associated with HDL-C, we provide evidence that this pharmacogenetic effect is independent of its association with baseline HDL-C levels.
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- White People
- Treatment Outcome
- Polymorphism, Single Nucleotide
- Pharmacogenomic Variants
- Male
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Humans
- Genome-Wide Association Study
- Genetics & Heredity
- Female
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- White People
- Treatment Outcome
- Polymorphism, Single Nucleotide
- Pharmacogenomic Variants
- Male
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Humans
- Genome-Wide Association Study
- Genetics & Heredity
- Female