Statin-associated muscle toxicity : clinical and genomic perspectives

Turner, R ORCID: 0000-0002-7315-679X (2017) Statin-associated muscle toxicity : clinical and genomic perspectives PhD thesis, University of Liverpool.

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Abstract

Statins are lipid-lowering agents and amongst the most commonly prescribed medications worldwide. Although generally well-tolerated, statins cause a range of adverse myotoxicity phenotypes ranging from mild myalgia to rare life-threatening rhabdomyolysis. The aetiology of statin-associated myotoxicity (SAM) is incompletely understood but clinical risk factors that increase systemic statin exposure (e.g. older age, drug interactions) have been identified. A common nonsynonymous variant (rs4149056, V174A) in the solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene that encodes the hepatocyte-specific sinusoidal influx transporter, organic anion-transporting polypeptide 1B1 (OATP1B1), is associated with increased statin exposure and simvastatin myopathy. The aims of this thesis were to: examine whether muscular complaints impact statin use, assess if suboptimal statin use affects cardiovascular events, and investigate statin pharmacogenomics using both the hepatic reductase null (HRN) mouse model and the Pharmacogenetics of Acute Coronary Syndrome (PhACS) study, which was a UK multicentre prospective observational study of non-ST elevation ACS patients (n=1,470). One month after hospitalisation, ... (continues)

Item Type:	Thesis (PhD)
Divisions:	Faculty of Health & Life Sciences
Depositing User:	Symplectic Admin
Date Deposited:	22 Aug 2018 08:57
Last Modified:	07 Feb 2025 13:25
DOI:	10.17638/03020572
Supervisors:	Pirmohamed, Munir ORCID: 0000-0002-7534-7266 Morris, Andrew Carr, Dan Kitteringham, Neil
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3020572
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