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Revista chilena de cardiología
versión On-line ISSN 0718-8560
ROSALES Z, Alexy y SALAZAR, Luis A. Effect of ABCB1 and CYP3A4 gene polymorphisms on the therapeutic response to atorvastatin in Chilean hypercholesterolemic individuals. Rev Chil Cardiol [online]. 2011, vol.30, n.2, pp.113-122. ISSN 0718-8560. http://dx.doi.org/10.4067/S0718-85602011000200004.
Background: : statins are effective in the control of hypercholesterolemia. However, the therapeutic response to these drugs presents a great inter-individual variability. Factors such as age, gender and ethnicity have been associated to this variability. Recent studies show that polymorphisms can influence the lipid-lowe-ring response to statins. The aim of the present study was to investigate the effect of three polymorphisms 3435C>T (ABCB1), 2677G>A/T (ABCB1) and -290 A>G (CYP3A4) gene on the response to atorvastatin treatment in Chilean hypercholesterolemic individuals. Methods: 94 hypercholesterolemic individuals, were treated with atorvastatin, 10mg/day for 4 weeks. We determined serum levels of total cholesterol, HDL-c, LDL-c and triglycerides, before and after treatment. The polymorphisms were analyzed by PCR-RFLP. Results: Significant reductions were observed in total cholesterol (275 ± 18 vs. 235 ± 22 mg/dL, p<0.001), LDL-c (183 ± 16 vs. 146 ± 24 mg/dL, p<0.001) and triglycerides levels (225 ± 48 vs. 172 ± 51 mg/dL, polymorphisms on the therapeutic hypercholesterolemic individuals p<0.001). In addition, an increase in the HDL-C levels was observed (47 ± 10 vs. 55 ± 7, p<0.001). The genotype distribution for 3535C>T variant of ABCB1 gene was: CC=47.9%, CT=41.5% and TT=10.6%. The genotype distribution for 2677G>A/T polymorphism (ABCB1) was AA=1.1%, GA=14.9%, GT=28.7%, TA=9.6%, TT=8.5% and GG=37.2%. The genotype distribution for -290A>G variant of CYP3A4 gene was: AA=77.7%. AG=22.3% and GG=0.0 %. Subjects carrying the G allele for the -290 A>G variant of the CYP3A4 gene, exhibited a greater reduction in total cholesterol (p=0.001) and LDL-C levels (p<0.001). No differences were observed for the other polymorphisms studied. Conclusion: This study suggests that the therapeutic response to atorvastatin (10mg/day during 4 weeks) is influenced by the -290 A>G variant of CYP3A4 gene.
Palabras clave : Polymorphisms; CYP3A4; atorvastatin; ABCB1.