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(TTA)n polymorphism in 3-hydroxy-3-methylglutaryl-coenzyme A and response to atorvastatin in coronary artery disease

Viviana Noriega1, Christian Pennanen, María Pilar Sánchez

  • 1FONDAP Center for Molecular Cell Studies, Clinical Hospital, University of Chile, Santiago, Chile.

Basic & Clinical Pharmacology & Toxicology
|December 11, 2008
PubMed

Insights

Atorvastatin effectively lowers cholesterol regardless of HMGCR (TTA)n gene variations. This study found no significant differences in low-density lipoprotein cholesterol reduction based on this genetic polymorphism in coronary artery disease patients.

Area of Science:

  • Pharmacogenomics
  • Cardiovascular Medicine
  • Biochemistry

Background:

  • 3-Hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibitors are crucial for managing dyslipidemia.
  • Individual responses to statin therapy vary, often linked to genetic factors.
  • The HMGCR (TTA)n polymorphism is a candidate for influencing statin efficacy.

Purpose of the Study:

  • To investigate the association between the HMGCR (TTA)n polymorphism and atorvastatin's efficacy in reducing low-density lipoprotein cholesterol (LDL-C) in patients with coronary artery disease.
  • To evaluate the impact of this polymorphism on other lipid and inflammatory markers.

Main Methods:

  • An open-label study involving 64 coronary artery disease patients treated with 40 mg of atorvastatin daily for 8 weeks.
  • Genotyping for the HMGCR (TTA)n polymorphism using polymerase chain reaction.
  • Assessment of changes in total cholesterol, triglycerides, high-sensitivity C-reactive protein (hs-CRP), and free F(2)-isoprostanes.

Main Results:

  • Atorvastatin treatment led to significant reductions in LDL-C, total cholesterol, and free F(2)-isoprostanes across all HMGCR (TTA)n genotypes.
  • No significant differences in LDL-C reduction were observed between different allelic variants of the (TTA)n polymorphism.
  • Reductions in hs-CRP were noted in patients with >10/>10 and 10/10 genotypes.

Conclusions:

  • The HMGCR (TTA)n polymorphism does not appear to influence the effectiveness of atorvastatin in lowering LDL-C, total cholesterol, or triglycerides in this patient cohort.
  • While some inflammatory markers showed genotype-specific responses, the primary lipid-lowering effects of atorvastatin were consistent across different (TTA)n genotypes.

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