(TTA)n polymorphism in 3-hydroxy-3-methylglutaryl-coenzyme A and response to atorvastatin in coronary artery disease patients.
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.
Noriega
Viviana
V
FONDAP Center for Molecular Cell Studies, Clinical Hospital, University of Chile, Santiago, Chile.
Pennanen
Christian
C
Sánchez
María Pilar
MP
Chiong
Mario
M
Llancaqueo
Marcelo
M
Lavandero
Sergio
S
Prieto
Juan Carlos
JC
D000368:Aged; D000483:Alleles; D000069059:Atorvastatin; D002097:C-Reactive Protein / Q000187:drug effects / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011758:Pyrroles / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood; D018911:Trinucleotide Repeats / Q000235:genetics*
D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D014280:Triglycerides; D002097:C-Reactive Protein; D002784:Cholesterol; D000069059:Atorvastatin; D006903:Hydroxymethylglutaryl CoA Reductases