J Appl Biomed 10:19-28, 2012 | DOI: 10.2478/v10136-012-0001-3

Variant within CELSR2/PSRC1/SORT1, but not within CILP2/PBX4, PCSK9 and APOB genes, has a potential to influence statin treatment efficacy

Jaroslav Alois Hubáček^1,2,*, Věra Adámková^1,2, Věra Lánská¹, Dana Dlouhá¹, Jitka Rynekrová¹, Lukáš Zlatohlávek³, Martina Prusíková³, Richard Češka³, Michal Vrablík³

¹ Institute for Clinical and Experimental Medicine, Prague, Czech Republic

² University of South Bohemia, Faculty of Health and Social Studies, České Budějovice, Czech Republic

³ 3rd Department of Internal Medicine, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic

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 this inter-individual difference can be explained by genetic factors. Using the GWA approach, candidate genes that may modify the response to statin treatment have been detected. Variants rs646776 (CELSR2/PSRC1/SORT1), rs16996148 (CILP2/PBX4), rs11206510 (PCSK9) and rs693 (APOB) were analysed 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 available prior to and after 8-12 weeks of therapy. There was a significant decrease both in the total (7.36±1.28→5.43±1.01 mmol/l) and LDL-cholesterol (4.72±1.35→3.19±0.98 mmol/l) after treatment. The genotype 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 compared to common homozygotes (LDL-cholesterol, Δ -20.3% vs. Δ -32.0%). No other significant associations with lipid changes were detected. Together with variations of other, multiple gene loci the variant at CELSR2/PSRC1/SORT1 gene cluster may be useful for individualization of statin treatment leading to better outcomes of the treatment.

Keywords: dyslipidemia; statins; gene variants; pharmacogenetics; treatment efficacy; CELSR2, PSRC1, SORT1; CILP2, PBX4; PCSK9; APOB

Received: July 29, 2011; Revised: September 20, 2011; Published: March 31, 2012  Show citation