Correlation Engine 2.0
Clear Search sequence regions


Sizes of these terms reflect their relevance to your search.

The ability of statins to strongly reduce low-density lipoprotein cholesterol (LDL-C) varies interindividually and is partially influenced by genetic variants. Based on a comprehensive analysis of 23 single nucleotide polymorphisms (SNPs) known to be associated with pharmacokinetics and dynamics of statins, we developed a genetic risk score to study its impact on the therapy outcome in elderly individuals under at least 5 years statin therapy. The study was performed in a population-based cohort of 1016 elderly individuals, which comprised 168 statin users investigated at age 75 and 80. Using random forest models, the major variants influencing LDL-C levels were summarized in a weighted GRS (wGRS). The wGRS was tested with lipid and glucose outcomes and validated in an independent population-based cohort including 221 statin users. Four SNPs within the APOE cluster (rs7412, rs4420638), ABCC2 (rs2002042) and CELSR/SORT1/PSRC1 (rs646776), displayed a major impact on statin efficacy. The wGRS was significantly associated with lower LDL-C at age 75 and 80. This association was replicated displaying similar results. GRS analysis is a powerful tool to evaluate the additive effects of genetic variants on statin response and to estimate the magnitude of LDL-C reduction to a considerable extent in the older population. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Citation

D M Ciuculete, M Bandstein, C Benedict, G Waeber, P Vollenweider, L Lind, H B Schiöth, J Mwinyi. A genetic risk score is significantly associated with statin therapy response in the elderly population. Clinical genetics. 2017 Mar;91(3):379-385

Expand section icon Mesh Tags

Expand section icon Substances


PMID: 27943270

View Full Text