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

Hamrefors, Viktor; Orho-Melander, Marju LU ; Krauss, Ronald M; Hedblad, Bo LU ; Almgren, Peter LU ; Berglund, Göran LU and Melander, Olle LU (2010) In Journal of Lipid Research 51(3). p.625-634
Abstract
While conventional pharmacogenetic studies have considered single gene effects, we tested if a genetic score of nine LDL- and HDL-associated SNPs, 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 one year fluvastatin treatment. In women, increasing number of... (More)
While conventional pharmacogenetic studies have considered single gene effects, we tested if a genetic score of nine LDL- and HDL-associated SNPs, 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 one year fluvastatin treatment. In women, 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) was 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Lipid Research
volume
51
issue
3
pages
625 - 634
publisher
American Society for Biochemistry and Molecular Biology
external identifiers
  • wos:000274513300019
  • pmid:19773416
  • scopus:77950624935
ISSN
1539-7262
DOI
10.1194/jlr.P001792
language
English
LU publication?
yes
id
22020190-1be2-48ee-bfb5-78dfbb099c62 (old id 1483229)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19773416?dopt=Abstract
date added to LUP
2010-03-17 10:45:51
date last changed
2018-05-29 09:27:49
@article{22020190-1be2-48ee-bfb5-78dfbb099c62,
  abstract     = {While conventional pharmacogenetic studies have considered single gene effects, we tested if a genetic score of nine LDL- and HDL-associated SNPs, 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 one year fluvastatin treatment. In women, 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) was 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.},
  author       = {Hamrefors, Viktor and Orho-Melander, Marju and Krauss, Ronald M and Hedblad, Bo and Almgren, Peter and Berglund, Göran and Melander, Olle},
  issn         = {1539-7262},
  language     = {eng},
  number       = {3},
  pages        = {625--634},
  publisher    = {American Society for Biochemistry and Molecular Biology},
  series       = {Journal of Lipid Research},
  title        = {A gene score of nine LDL and HDL regulating genes is associated with fluvastatin induced cholesterol changes in women.},
  url          = {http://dx.doi.org/10.1194/jlr.P001792},
  volume       = {51},
  year         = {2010},
}