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Single nucleotide polymorphisms in genes that are associated with a modified response to statin therapy: the Rotterdam Study

Abstract

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.

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Acknowledgements

This work was supported by the Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO; 050-060-810). The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly; the Ministry of Education, Culture and Science; the Ministry of Health Welfare and Sports; the European Commission and the Municipality of Rotterdam. AH Maitland-van der Zee was funded by a Veni grant from the NWO.

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Correspondence to B H Ch Stricker.

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de Keyser, C., Eijgelsheim, M., Hofman, A. et al. Single nucleotide polymorphisms in genes that are associated with a modified response to statin therapy: the Rotterdam Study. Pharmacogenomics J 11, 72–80 (2011). https://doi.org/10.1038/tpj.2010.11

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