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(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 asses...

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Published in:Basic & clinical pharmacology & toxicology 2009-03, Vol.104 (3), p.211-215
Main Authors: Noriega, Viviana, Pennanen, Christian, Sánchez, María Pilar, Chiong, Mario, Llancaqueo, Marcelo, Lavandero, Sergio, Prieto, Juan Carlos
Format: Article
Language:English
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Summary::  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 F2‐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 F2‐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 F2‐isoprostane concentrations were not related to the presence of 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase polymorphism (TTA)n.
ISSN:1742-7835
1742-7843
DOI:10.1111/j.1742-7843.2008.00341.x