Rooted in Risk: Genetic Predisposition for Low-Density Lipoprotein Cholesterol Level Associates with Diminished Low-Density Lipoprotein Cholesterol Response to Statin Treatment

Abstract

Aims: To utilize previously reported lead SNPs for low-density lipoprotein cholesterol (LDL-c) levels to find additional loci of importance to statin response, and examine whether genetic predisposition to LDL-c levels associates with differential statin response. Methods: We investigated effects on statin response of 59 LDL-c SNPs, by combining summary level statistics from the Global Lipids Genetics and Genomic Investigation of Statin Therapy consortia. Results: Lead SNPs for APOE, SORT1 and NPC1L1 were associated with a decreased LDL-c response to statin treatment, as was overall genetic predisposition for increased LDL-c levels as quantified with 59 SNPs, with a 5.4% smaller statin response per standard deviation increase in genetically raised LDL-c levels. Conclusion: Genetic predisposition for increased LDL-c level may decrease efficacy of statin therapy.

Keywords::

• MR–Egger
• pharmacogenetics
• statin therapy

To view the supplementary data that accompany this paper please visit the journal website at:https://www.futuremedicine.com/doi/full/10.2217/pgs-2016-0091

Acknowledgements

The authors thank the Global lipids Genetic consortium for making the result files of their meta-analysis available. In addition, the authors wish to express our gratitude to all studies participating in the Genomic Investigation of Statin Therapy consortium.

Financial & competing interests disclosure

BM Psaty serves on the Data and Safety Monitoring Board of a clinical trial funded by the manufacturer, and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. DI Chasman received research support for independent genetic analysis in JUPITER from AstraZeneca. JW Jukema is an Established Clinical Investigator of The Netherlands Heart Foundation (grant no. 2001 D 032). RM Krauss serves on the Merck Global Atherosclerosis Advisory Board. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

BM Psaty serves on the Data and Safety Monitoring Board of a clinical trial funded by the manufacturer, and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. DI Chasman received research support for independent genetic analysis in JUPITER from AstraZeneca. JW Jukema is an Established Clinical Investigator of The Netherlands Heart Foundation (grant no. 2001 D 032). RM Krauss serves on the Merck Global Atherosclerosis Advisory Board. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.