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

Basic Clin Pharmacol Toxicol. 2009 Mar;104(3):211-5. doi: 10.1111/j.1742-7843.2008.00341.x. Epub 2008 Dec 3.

Abstract

3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors have been used clinically for lowering total and low-density lipoprotein cholesterol. Interindividual pharmacological differences observed with this treatment have been attributed to genetic differences. The aim of this study was to assess the association in the low-density lipoprotein cholesterol reduction by atorvastatin and (TTA)n polymorphism in the 3-hydroxy-3-methylglutaryl-coenzyme A reductase gene in patients with coronary artery disease. Changes in total cholesterol levels, triglycerides, high-sensitivity C-reactive protein and free F(2)-isoprostanes were also evaluated. In an open study, patients received 40 mg atorvastatin daily for 8 weeks. Genotyping was done through polymerase chain reaction. The genotype distribution of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase (TTA)n polymorphism was: >10/>10 in 22 out of 64 patients (34%), >10/10 in 14 out of 64 patients (22%) and 10/10 in 28 out of 64 patients (44%). The reduction of low-density lipoprotein cholesterol levels by atorvastatin was not different between allelic variants (TTA)n repeat polymorphism. Reductions in high-sensitivity C-reactive protein were observed in atorvastatin-treated patients with alleles >10/>10 and 10/10. Free F(2)-isoprostanes and total cholesterol were also significantly lower after treatment for all alleles, irrespective of type of polymorphism. In conclusion, the changes induced by atorvastatin treatment on low-density lipoprotein cholesterol, total cholesterol, triglycerides, high-sensitivity C-reactive protein and free F(2)-isoprostane concentrations were not related to the presence of 3-hydroxy-3-methylglutaryl-coenzyme A reductase polymorphism (TTA)n.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Atorvastatin
  • C-Reactive Protein / drug effects
  • C-Reactive Protein / metabolism
  • Cholesterol / blood
  • Cholesterol, LDL / blood
  • Cholesterol, LDL / drug effects
  • Coronary Artery Disease / drug therapy*
  • Coronary Artery Disease / genetics
  • Coronary Artery Disease / physiopathology
  • Female
  • Follow-Up Studies
  • Heptanoic Acids / pharmacology*
  • Humans
  • Hydroxymethylglutaryl CoA Reductases / genetics
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Pyrroles / pharmacology*
  • Triglycerides / blood
  • Trinucleotide Repeats / genetics*

Substances

  • Cholesterol, LDL
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Triglycerides
  • C-Reactive Protein
  • Cholesterol
  • Atorvastatin
  • Hydroxymethylglutaryl CoA Reductases