The CETP locus is the only genome-wide-significant genetic determinant of HDL-C response to statins, independent of baseline HDL-C, in a 27,720-person meta-analysis (J Med Genet 2016)

Original title: Meta-analysis of genome-wide association studies of HDL cholesterol response to statins

J Med Genet · 1 September 2016 · 7

Postmus I, Warren HR, Trompet S, Arsenault BJ, Avery CL, Bis JC, Chasman DI, de Keyser CE, Deshmukh HA, Evans DS, Feng Q, Li X et al.

Performing a meta-analysis of genome-wide association studies to find genetic variants affecting statin-induced HDL cholesterol change, researchers followed up the 123 most promising signals (p less than 1x10-4) from a first stage of 16 769 statin-treated participants in an independent group of 10 951 statin-treated individuals, for a total of 27 720 individuals. Minor alleles at the CETP locus were the only associations reaching genome-wide significance (p less than 5x10-8) for greater HDL-C response to statin treatment. The authors conclude CETP may be the only common-variant locus with a substantial detectable effect on statin-induced HDL-C response in people of European descent, and that this pharmacogenetic effect is independent of CETP's known association with baseline HDL-C levels.

Original abstract

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.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.