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,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. © journal of applied biomedicine.