A gene score of nine LDL and HDL regulating genes is associated with fluvastatin-induced cholesterol changes in women[S]
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 asymptoma...
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doaj-4d0327c7b29f4fb1ad844c9ef631a50b2021-04-28T05:55:32ZengElsevierJournal of Lipid Research0022-22752010-03-01513625634A gene score of nine LDL and HDL regulating genes is associated with fluvastatin-induced cholesterol changes in women[S]Viktor Hamrefors0Marju Orho-Melander1Ronald M. Krauss2Bo Hedblad3Peter Almgren4Göran Berglund5Olle Melander6Department of Clinical Sciences, Lund University, Malmö, SwedenDepartment of Clinical Sciences, Lund University, Malmö, SwedenChildren's Hospital, Oakland Research Institute, Oakland, CADepartment of Clinical Sciences, Lund University, Malmö, SwedenDepartment of Clinical Sciences, Lund University, Malmö, SwedenDepartment of Clinical Sciences, Lund University, Malmö, SwedenTo whom correspondence should be addressed; Department of Clinical Sciences, Lund University, Malmö, SwedenWhile 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.http://www.sciencedirect.com/science/article/pii/S0022227520305204genetic scorestatinspharmacogeneticsatherosclerosiscarotid plaquelipid levels |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Viktor Hamrefors Marju Orho-Melander Ronald M. Krauss Bo Hedblad Peter Almgren Göran Berglund Olle Melander |
spellingShingle |
Viktor Hamrefors Marju Orho-Melander Ronald M. Krauss Bo Hedblad Peter Almgren Göran Berglund Olle Melander A gene score of nine LDL and HDL regulating genes is associated with fluvastatin-induced cholesterol changes in women[S] Journal of Lipid Research genetic score statins pharmacogenetics atherosclerosis carotid plaque lipid levels |
author_facet |
Viktor Hamrefors Marju Orho-Melander Ronald M. Krauss Bo Hedblad Peter Almgren Göran Berglund Olle Melander |
author_sort |
Viktor Hamrefors |
title |
A gene score of nine LDL and HDL regulating genes is associated with fluvastatin-induced cholesterol changes in women[S] |
title_short |
A gene score of nine LDL and HDL regulating genes is associated with fluvastatin-induced cholesterol changes in women[S] |
title_full |
A gene score of nine LDL and HDL regulating genes is associated with fluvastatin-induced cholesterol changes in women[S] |
title_fullStr |
A gene score of nine LDL and HDL regulating genes is associated with fluvastatin-induced cholesterol changes in women[S] |
title_full_unstemmed |
A gene score of nine LDL and HDL regulating genes is associated with fluvastatin-induced cholesterol changes in women[S] |
title_sort |
gene score of nine ldl and hdl regulating genes is associated with fluvastatin-induced cholesterol changes in women[s] |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2010-03-01 |
description |
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. |
topic |
genetic score statins pharmacogenetics atherosclerosis carotid plaque lipid levels |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520305204 |
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