A gene score of nine LDL and HDL regulating genes is associated with fl uvastatin-induced cholesterol changes in women

Abstract

While conventional pharmacogenetic studies have considered single gene effects, we tested if a genetic score of nine LDL-and HDL-associated single nucleotide polymorphisms, previously shown to predict cardiovascular disease, is related to fl uvastatin-induced lipid change. In patients with asymptomatic plaque in the right carotid artery, thus candidates for statin therapy, we related score LDL [APOB(rs693), APOE(rs4420638), HMGCR(rs12654264), LDLR(rs1529729), and PCSK9(rs11591147)] and score HDL [ABCA1(rs3890182), CETP(rs1800775), LIPC (rs1800588), and LPL(rs328)] as well as the combined score LDL+HDL to fl uvastatin-induced LDL reduction (± metoprolol) (n = 395) and HDL increase (n = 187) following 1 year of fl uvastatin treatment. In women, an increasing number of unfavorable alleles (i.e., alleles conferring higher LDL and lower HDL) of score LDL+HDL (P = 0.037) and of score LDL (P = 0.023) was associated with less pronounced fl uvastatin-induced LDL reduction. Furthermore, in women, both score LDL+HDL (P = 0.001) and score HDL (P = 0.022) were directly correlated with more pronounced fl uvastatin-induced HDL increase, explaining 5.9-11.6% of the variance in treatment response in women. There were no such associations in men. This suggests that a gene score based on variation in nine different LDL-and HDL-associated genes is of importance for the magnitude of fl uvastatin HDL increase in women with asymptomatic plaque in the carotid artery. Copyright © 2010 by the American Society for Biochemistry and Molecular Biology, Inc.