%0 Journal Article
%T Variant within CELSR2/PSRC1/SORT1, but not within CILP2/PBX4, PCSK9 and APOB genes, has a potential to influence statin treatment efficacy
%A Jaroslav Alois Hubacek
%A Vera Adamkov¨¢
%A Vera Lanska
%A Dana Dlouha
%J Journal of Applied Biomedicine
%@ 1214-0287
%D 2012
%I 
%X Statins have become a cornerstone of cardiovascular prevention. However, their lipid lowering efficacy and,thus also, impact on event risk reduction, differ substantially between individuals. The major part of thisinter-individual difference can be explained by genetic factors. Using the GWA approach, candidate genesthat may modify the response to statin treatment have been detected. Variants rs646776(CELSR2/PSRC1/SORT1), rs16996148 (CILP2/PBX4), rs11206510 (PCSK9) and rs693 (APOB) wereanalysed in 370 (146 males) dyslipidemic patients treated with statins (46.6% simvastatin, 41.5% atorvastatin,11.9% lovastatin, 10 or 20 mg/day) and 470 normolipidemic controls (188 males). Lipid levels were availableprior to and after 8¨C12 weeks of therapy. There was a significant decrease both in the total(7.36¡À1.28 5.43¡À1.01 mmol/l) and LDL-cholesterol (4.72¡À1.35 3.19¡À0.98 mmol/l) after treatment. Thegenotype frequencies of the three SNPs differed between patients and controls (rs646776, rs16996148, rs693).The carriers of the minor rs599838 genotype had a significantly lower response to statin treatment comparedto common homozygotes (LDL-cholesterol, ¦¤ ¨C20.3% vs. ¦¤ ¨C32.0%). No other significant associations withlipid changes were detected. Together with variations of other, multiple gene loci the variant atCELSR2/PSRC1/SORT1 gene cluster may be useful for individualization of statin treatment leading to betteroutcomes of the treatment.
%K dyslipidemia
%K statins
%K gene variants
%K pharmacogenetics
%K treatment efficacy
%K CELSR2/PSRC1/SORT1
%K CILP2/PBX4
%K PCSK9
%K APOB
%U http://www.zsf.jcu.cz/jab/10_1/hubacek.pdf