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The objective of this study was to investigate whether common variation in genes involved in lipid metabolism modify the effect of statins on serum total cholesterol concentration. Statin users were identified in the Rotterdam Study, a prospective population-based cohort study of subjects >55 years of age. We studied the association between single nucleotide polymorphisms (SNPs) in genes involved in lipid metabolism and total cholesterol response to statin therapy, using linear regression analysis and adjusting for potential confounders. Replication was performed in an independent extended cohort of the Rotterdam Study. Genotype data and total cholesterol concentrations after start of statin therapy were available for 554 newly started statin users. Two SNPs were associated with a significantly higher cholesterol concentration under statin therapy: SNP rs1532624 in the CETP gene (β: 0.141  mmol l(-1), P=0.004 per additional allele) and SNP rs533556 in the APOA1 gene (β: 0.138  mmol l(-1), P=0.005 per additional allele). In the replication sample, only the CETP rs1532624 SNP again showed a significant association. The SNPs were not related to baseline total cholesterol in non-statin users. In conclusion, we found that the CETP rs1532624 polymorphism is associated with cholesterol response to statin therapy in a cohort of elderly subjects in the general population.

Original publication

DOI

10.1038/tpj.2010.11

Type

Journal article

Journal

Pharmacogenomics J

Publication Date

02/2011

Volume

11

Pages

72 - 80

Keywords

Aged, Cholesterol, Cohort Studies, Female, Genetic Variation, Genotype, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Linear Models, Lipid Metabolism, Male, Middle Aged, Polymorphism, Single Nucleotide, Prospective Studies