Genetic Polymorphisms and Statin-Associated Side Effects: The Role of SLCO1B1 and Additional Risk Factors

Romana Marušić; Tatjana Bačun; Dunja Šojat; Saška Marczi

doi:10.26332/jp55ha33

Authors

Romana Marušić Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia; Department of Internal Medicine, National Memorial Hospital "Dr Juraj Njavro", Vukovar, Croatia Author https://orcid.org/0000-0003-0392-2943
Tatjana Bačun Department of Internal Medicine and History of Medicine, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia; Department of Clinical Medicine, Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia; Division of Endocrinology, Department of Internal Medicine, University Hospital Centre Osijek, Osijek, Croatia Author https://orcid.org/0000-0001-7012-5325
Dunja Šojat Health Center of Osijek-Baranja County, Osijek, Croatia; Department of Family Medicine, Faculty of Medicine, Josip Juraj Strossmayer University Osijek, Osijek, Croatia Author https://orcid.org/0000-0001-7269-3334
Saška Marczi Clinical Department of Transfusion Medicine, University Hospital Centre Osijek, Osijek, Croatia; Department of Medical Chemistry, Biochemistry and Clinical Chemistry, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia Author https://orcid.org/0000-0003-2110-3327

DOI:

https://doi.org/10.26332/jp55ha33

Keywords:

hydroxymethylglutaryl-CoA reductase inhibitors, SLCO1B1 gene, hypercholesterolemia

Abstract

Statins are first-line agents for managing dyslipidemia, primarily prescribed to reduce low-density lipoprotein cholesterol (LDL-C) and prevent atherosclerotic cardiovascular disease (ASCVD). Despite their proven efficacy, there is significant interindividual variability in statin response, with some patients experiencing adverse events such as statin-associated muscle symptoms (SAMS) and hepatotoxicity. These effects are partly attributable to genetic polymorphisms, particularly in the SLCO1B1 gene, which encodes the organic anion-transporting polypeptide 1B1 (OATP1B1) responsible for hepatic statin uptake. The SLCO1B1 rs4149056 polymorphism is associated with impaired transporter function, leading to elevated statin plasma concentrations and a higher risk of statin-induced myopathy, especially with simvastatin. Non-genetic factors, such as hypothyroidism, can exacerbate statin intolerance by impairing lipid metabolism and increasing the risk of myopathy and rhabdomyolysis due to reduced hepatic statin clearance. Vitamin D deficiency has also been linked to increased susceptibility to SAMS, as vitamin D plays a role in muscle function and statin metabolism through CYP enzyme modulation. Coenzyme Q10 (CoQ10) depletion, a consequence of statin therapy due to inhibition of the mevalonate pathway, may further contribute to mitochondrial dysfunction and muscle injury. Incorporating pharmacogenetic testing and addressing modifiable risk factors such as thyroid dysfunction and vitamin D deficiency may optimize statin therapy, reducing adverse effects while maintaining cardiovascular protection.

Keywords: hydroxymethylglutaryl-CoA reductase inhibitors; SLCO1B1 gene; hypercholesterolemia; myopathy, statin-induced; pharmacogenomics

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