A gene score of nine LDL and HDL regulating genes is associated with fluvastatin induced cholesterol changes in women.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1483229
- author
- Hamrefors, Viktor LU ; Orho-Melander, Marju LU ; Krauss, Ronald M ; Hedblad, Bo LU ; Almgren, Peter LU ; Berglund, Göran LU and Melander, Olle LU
- organization
- publishing date
- 2010
- 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
- pmid:19773416
- 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
- 2016-04-01 09:57:30
- date last changed
- 2024-03-23 22:14:48
@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}}, doi = {{10.1194/jlr.P001792}}, volume = {{51}}, year = {{2010}}, }