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.
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; Smit, RAJ; Smith, AV; Sun, F; Taylor, KD; Arnold, AM; Barnes, MR; Barratt, BJ; Betteridge, J; Boekholdt, SM; Boerwinkle, E; Buckley, BM; Chen, Y-DI; de Craen, AJM; Cummings, SR; Denny, JC; Dubé, MP; Durrington, PN; Eiriksdottir, G; Ford, I; Guo, X; Harris, TB; Heckbert, SR; Hofman, A; Hovingh, GK; Kastelein, JJP; Launer, LJ; Liu, C-T; Liu, Y; Lumley, T; McKeigue, PM; Munroe, PB; Neil, A; Nickerson, DA; Nyberg, F; O'Brien, E; O'Donnell, CJ; Post, W; Poulter, N; Vasan, RS; Rice, K; Rich, SS; Rivadeneira, F; Sattar, N; Sever, P; Shaw-Hawkins, S; Shields, DC; Slagboom, PE; Smith, NL; Smith, JD; Sotoodehnia, N; Stanton, A; Stott, DJ; Stricker, BH; Stürmer, T; Uitterlinden, AG; Wei, W-Q; Westendorp, RGJ; Whitsel, EA; Wiggins, KL; Wilke, RA; Ballantyne, CM; Colhoun, HM; Cupples, LA; Franco, OH; Gudnason, V; Hitman, G; Palmer, CNA; Psaty, BM; Ridker, PM; Stafford, JM; Stein, CM; Tardif, J-C; Caulfield, MJ; Jukema, JW; Rotter, JI; Krauss, RM
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