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Published on: April 1, 2019

The C3435T polymorphism in ABCB1 influences atorvastatin efficacy and muscle symptoms in a high-risk vascular cohort

Michel R Hoenig1, Philip J Walker, Christine Gurnsey

  • 1Royal Brisbane and Women's Hospital, University of Queensland Centre for Clinical Research, Building 71, Herston Qld 4029, Australia. drmhoenig@yahoo.com.au

Journal of Clinical Lipidology
|March 12, 2011
PubMed

Insights

The CC genotype of the ABCB1 C3435T polymorphism is linked to reduced atorvastatin efficacy and increased myalgia risk. This finding is independent of cholesterol metabolism, highlighting genetic factors in statin response.

Area of Science:

  • Pharmacogenomics
  • Cardiovascular Medicine
  • Biochemistry

Background:

  • The ABCB1 gene encodes P-glycoprotein, a transporter influencing drug pharmacokinetics.
  • The C3435T polymorphism in ABCB1 is associated with varying P-glycoprotein expression levels.
  • Previous studies suggest a link between the CC genotype and reduced response to statins like atorvastatin.

Purpose of the Study:

  • To investigate the association between the ABCB1 C3435T polymorphism and atorvastatin efficacy, independent of cholesterol metabolism.
  • To determine if the C3435T genotype influences the incidence of myalgia in patients treated with atorvastatin.

Main Methods:

  • Genotyping of the ABCB1 C3435T polymorphism in high-risk vascular patients.
  • Treatment with atorvastatin 80 mg daily for six weeks.
  • Analysis of lipid panels, LDL-C reduction, and myalgia incidence in relation to genotype.

Main Results:

  • Patients with the CC genotype exhibited a significantly lower reduction in LDL-C compared to TT/TC genotypes (53% vs. 59%, P=.034).
  • This reduced efficacy was independent of variations in cholesterol metabolism (P=.045 after correction).
  • The T allele was more frequent in patients experiencing myalgia (0.80 vs. 0.62, P=.043).

Conclusions:

  • The CC genotype at the ABCB1 C3435T polymorphism is associated with diminished atorvastatin efficacy, irrespective of cholesterol metabolism.
  • A higher frequency of the T allele and lower frequency of the C allele were observed in patients reporting myalgia.
Abstract

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