(TTA)n Polymorphism in 3-Hydroxy-3-Methylglutaryl-Coenzyme A and Response to Atorvastatin in Coronary Artery Disease Patients

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.