Meta-analysis of genome-wide association studies of HDL cholesterol response to statins.

J Med Genet 2016 12 1;53(12):835-845. Epub 2016 Sep 1.

Department of Atherosclerosis Research, Children's Hospital Oakland Research Institute, Oakland, California, USA.

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 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) 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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http://dx.doi.org/10.1136/jmedgenet-2016-103966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5309131PMC
December 2016
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References

(Supplied by CrossRef)
Comparative effects of lipid-lowering therapies
Davidson et al.
Prog Cardiovasc Dis 2004

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