National Cholesterol Awareness Month Identification of Genetic Variants Associated With Response to Statin Therapy

Objective—The purpose of this study was to test the association between polymorphisms in genes involved in either LDL cholesterol (LDL-C) metabolism or statin pharmacokinetics and LDL-C reduction with statins. Methods and Results—49 tagging and candidate polymorphisms in 9 genes were genotyped in 1507 post-ACS subjects randomized to atorvastatin or pravastatin. Two polymorphisms (rs7412, rs429358) that define the 2, 3, and 4 isoforms of apolipoprotein E were significantly associated with percent reduction in LDL-C with atorvastatin ( 2 carriers 53.8%, 3/ 3 48.1%, and 4 carriers 46.4%, respectively, P 0.00039) and replicated in the pravastatin arm ( 2 carriers 22.1%, 3/ 3 21.8%, and 4 carriers 16.6%, respectively, P 0.00038). The proportion of subjects achieving an LDL-C 70 mg/dL at day 30 was higher for 2 than 4 carriers (P 1.3 10 ). In the pravastatin group, the triallelic rs2032582 variant (G2677T/A) in ABCB1 was associated with the percent reduction in LDL-C (GG 23.3%, non-G heterozygote 20.3%, and non-G homozygote 17.4%, P 0.042). Conclusion—Carriers of APOE 2 versus 4 had significantly greater LDL-C reduction with atorvastatin and with pravastatin, and more frequently achieved a guideline-recommended LDL-C 70 mg/dL. Polymorphisms in triallelic G2677T/A variant in ABCB1 were associated with the degree of LDL-C lowering with pravastatin. (Arterioscler Thromb Vasc Biol. 2009;29:1310-1315.)