Journal article

A statin-dependent QTL for GATM expression is associated with statin-induced myopathy

Lara M Mangravite, Barbara E Engelhardt, Marisa W Medina, Joshua D Smith, Christopher D Brown, Daniel I Chasman, Brigham H Mecham, Bryan Howie, Heejung Shim, Devesh Naidoo, QiPing Feng, Mark J Rieder, Yii-Der I Chen, Jerome I Rotter, Paul M Ridker, Jemma C Hopewell, Sarah Parish, Jane Armitage, Rory Collins, Russell A Wilke Show all

NATURE | NATURE PUBLISHING GROUP | Published : 2013

Abstract

Statins are prescribed widely to lower plasma low-density lipoprotein (LDL) concentrations and cardiovascular disease risk and have been shown to have beneficial effects in a broad range of patients. However, statins are associated with an increased risk, albeit small, of clinical myopathy and type 2 diabetes. Despite evidence for substantial genetic influence on LDL concentrations, pharmacogenomic trials have failed to identify genetic variations with large effects on either statin efficacy or toxicity, and have produced little information regarding mechanisms that modulate statin response. Here we identify a downstream target of statin treatment by screening for the effects of in vitro sta..

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University of Melbourne Researchers

Grants

Awarded by US National Institutes of Health (NIH)


Awarded by NIH


Awarded by Medical Research Council


Awarded by NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES


Awarded by NATIONAL HEART, LUNG, AND BLOOD INSTITUTE


Awarded by NATIONAL HUMAN GENOME RESEARCH INSTITUTE


Awarded by NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES


Funding Acknowledgements

This project was funded by a grant from the US National Institutes of Health (NIH), U01 HL69757. B.E.E. was funded through the Bioinformatics Research Development Fund, supported by K. and G. Gould and NIH grant K99/R00HG006265. M.S. was funded by NIH grant HG002585. We acknowledge the efforts of T. Kitchner and R. Mareedu for case validation in the Marshfield cohort. SEARCH was supported by the Medical Research Council, British Heart Foundation, National Health Service Genetic Knowledge Park, Centre National de Genotypage and Merck. The Heart Protection Study was funded by grants from the Medical Research Council, British Heart Foundation, Roche Vitamins and Merck. J.C.H. acknowledges support from the BHF Centre of Research Excellence, Oxford, UK. Genetic analysis in JUPITER was funded by a grant from AstraZeneca to D.I.C. and P.M.R.