Atorvastatin-associated rhabdomyolysis in a patient with a novel variant of the SLCO1B1 gene: A case report.
J Clin Lipidol
; 16(1): 23-27, 2022.
Article
em En
| MEDLINE
| ID: mdl-34887219
ABSTRACT
We report the case of an individual with severe hypercholesterolemia who experienced rhabdomyolysis with high dose atorvastatin. Genetic testing was undertaken to evaluate for suspected familial hypercholesterolemia (FH) and for the presence of gene variants associated with susceptibility to statin associated muscle disease. Genetic testing identified the presence of a potentially damaging variant of the hepatic xenobiotic transporter pump SLCO1B1, a single nucleotide variant (SNV) (rs77271279, c.481+1G>T) that disrupts the canonical donor splice motif. Although this variant has not previously been reported as associated with rhabdomyolysis and thus requires validation in population studies, it likely played a role in this patient's susceptibility to rhabdomyolysis based on functional assessment of the effect of this variant on SLCO1B1 protein function and given the known role of this transporter in statin uptake by the liver. The presence of this gene variant reinforced our decision to treat the patient's hypercholesterolemia with non-statin alternatives (PCSK9 inhibitor and ezetimibe). Genetic testing also identified the presence of a second SLCO1B1 gene variant, c.1200C>G (p.Phe400Leu, rs59113707) and homozygosity for an intron variant of the apolipoprotein(a) (LPA) gene (c.2604.138G>A intron variant, rs9457951) associated with increased Lp(a), a risk factor for atherosclerotic cardiovascular disease. Notably, all three variants are rare in persons of European descent but more frequent in African-Americans. These findings underscore the role of disabling mutations of the SLCO1B1 gene in statin myopathy and the need to validate these and other gene variants associated with statin myopathy in a population of patients with statin-associated muscle disease.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Rabdomiólise
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Inibidores de Hidroximetilglutaril-CoA Redutases
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Hipercolesterolemia
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Doenças Musculares
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
J Clin Lipidol
Assunto da revista:
BIOQUIMICA
/
METABOLISMO
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos