A gene score of nine LDL and HDL regulating genes is associated with fluvastatin-induced cholesterol changes in women.
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.
Department of Clinical Sciences, Lund University, Malmö, Sweden.
Viktor
V
Hamrefors
Marju
M
Orho-Melander
Ronald M
RM
Krauss
Bo
B
Hedblad
Peter
P
Almgren
Göran
G
Berglund
Olle
O
Melander
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D008076:Cholesterol, HDL / Q000235:genetics* / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000235:genetics* / Q000378:metabolism*; D015331:Cohort Studies; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D005260:Female; D000077340:Fluvastatin; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012727:Sex Characteristics
D000319:Adrenergic beta-Antagonists; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D000077340:Fluvastatin