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

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 RA, Smith AV, Sun F, Taylor KD, Arnold AM, Barnes MR, Barratt BJ, Betteridge J, Boekholdt SM, Boerwinkle E, Buckley BM, Chen YI, de Craen AJ, Cummings SR, Denny JC, Dubé MP, Durrington PN, Eiriksdottir G, Ford I, Guo X, Harris TB, Heckbert SR, Hofman A, Hovingh GK, Kastelein JJ, Launer LJ, Liu CT, 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 WQ, Westendorp RG, Whitsel EA, Wiggins KL, Wilke RA, Ballantyne CM, Colhoun HM, Cupples LA, Franco OH, Gudnason V, Hitman G, Palmer CN, Psaty BM, Ridker PM, Stafford JM, Stein CM, Tardif JC, Caulfield MJ, Jukema JW, Rotter JI, Krauss RM
J Med Genet. 2016 53 (12): 835-845

PMID: 27587472 · PMCID: PMC5309131 · DOI:10.1136/jmedgenet-2016-103966

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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MeSH Terms (11)

Cholesterol, HDL Cholesterol Ester Transfer Proteins European Continental Ancestry Group Female Genome-Wide Association Study Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors Male Pharmacogenomic Variants Polymorphism, Single Nucleotide Treatment Outcome

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