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

J Lipid Res. 2010 Mar;51(3):625-34. doi: 10.1194/jlr.P001792. Epub 2009 Sep 22.

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 fluvastatin-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 fluvastatin-induced LDL reduction (+/- metoprolol) (n = 395) and HDL increase (n = 187) following 1 year of fluvastatin 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 fluvastatin-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 fluvastatin-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 fluvastatin HDL increase in women with asymptomatic plaque in the carotid artery.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology
  • Cholesterol, HDL / genetics*
  • Cholesterol, HDL / metabolism*
  • Cholesterol, LDL / genetics*
  • Cholesterol, LDL / metabolism*
  • Cohort Studies
  • Fatty Acids, Monounsaturated / pharmacology*
  • Female
  • Fluvastatin
  • Humans
  • Indoles / pharmacology*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Sex Characteristics

Substances

  • Adrenergic beta-Antagonists
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Fatty Acids, Monounsaturated
  • Indoles
  • Fluvastatin