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Olle Melander

Principal investigator

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

Author

  • Viktor Hamrefors
  • Marju Orho-Melander
  • Ronald M Krauss
  • Bo Hedblad
  • Peter Almgren
  • Göran Berglund
  • Olle Melander

Summary, in English

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.

Department/s

  • EXODIAB: Excellence in Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health
  • Cardiovascular Research - Hypertension
  • Genomics, Diabetes and Endocrinology
  • Cardiovascular Research - Epidemiology
  • Internal Medicine - Epidemiology

Publishing year

2010

Language

English

Pages

625-634

Publication/Series

Journal of Lipid Research

Volume

51

Issue

3

Document type

Journal article

Publisher

American Society for Biochemistry and Molecular Biology

Topic

  • Cardiac and Cardiovascular Systems

Status

Published

Research group

  • Cardiovascular Research - Hypertension
  • Genomics, Diabetes and Endocrinology
  • Cardiovascular Research - Epidemiology
  • Internal Medicine - Epidemiology

ISBN/ISSN/Other

  • ISSN: 1539-7262