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

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, Delta-20.3% vs. Delta-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.