Frequency of Common Variants in Genes Involved in Lipid-Lowering Response to Statins in Chilean Subjects with Hypercholesterolemia

Interindividual differences in activity and expression of the metabolizing enzymes cytochrome P450 (CYP) 3A4 and 3A5 and the multidrug efflux pump P-glycoprotein (P-gp, encoded by ABCB1 gene) contribute considerably to lipid-lowering efficacy of statin treatment in subjects with hypercholesterolemia...

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Autores principales:	Rosales,Alexy, Pacheco,Alejandro, Cuevas,Alejandro, Saavedra,Nicolás, Zambrano,Tomás, Lanas,Fernando, Salazar,Luis A
Lenguaje:	English
Publicado:	Sociedad Chilena de Anatomía 2011
Materias:	Polymorphisms Statins Hypercholesterolemia ABCB1
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-95022011000400037
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spelling	oai:scielo:S0717-950220110004000372012-07-30Frequency of Common Variants in Genes Involved in Lipid-Lowering Response to Statins in Chilean Subjects with HypercholesterolemiaRosales,AlexyPacheco,AlejandroCuevas,AlejandroSaavedra,NicolásZambrano,TomásLanas,FernandoSalazar,Luis A Polymorphisms Statins Hypercholesterolemia ABCB1 Interindividual differences in activity and expression of the metabolizing enzymes cytochrome P450 (CYP) 3A4 and 3A5 and the multidrug efflux pump P-glycoprotein (P-gp, encoded by ABCB1 gene) contribute considerably to lipid-lowering efficacy of statin treatment in subjects with hypercholesterolemia. Variability in the activity of CYP3A4, CYP3A5 and P-gp could be considered to result from genetic polymorphisms encoding their genes. However, the available data indicate that the frequencies of ABCB1, CYP3A4 and CYP3A5 gene polymorphisms differ significantly across populations. Thus, the aim of the present study was to determine the allelic frequency of three common variants of these genes in Chilean individuals with primary hypercholesterolemia (HC) and controls. A total of 135 unrelated patients (44 ± 7 years old) with diagnosis of hypercholesterolemia (Total cholesterol 240 mg/dL) and 120 normolipidemic healthy controls (40 ± 10 years old; total cholesterol 200 mg/dL) were included in this study. The 3435C>T (MDR1), -290A>G (CYP3A4) and 6986A>G (CYP3A5) gene polymorphisms were analyzed by PCR-RFLP. The genotype distribution for 3435C>T variant of ABCB1 in HC patients (CC: 49%, CT: 37%, TT: 14%) and controls (CC: 41%, CT: 48%, TT: 11%) was comparable (P=0.186). Similarly, the genotype distribution for -290A>G polymorphism of CYP3A4 in HC subjects (AA: 73%, AG: 27%, GG: 0%) and controls (AA: 71%, AG: 29%, GG: 0%) was equivalent (P = 0.863). Finally, the genotype distribution for 6986A>G variant of CYP3A5 in HC individuals (AA: 4%, AG: 41%, GG: 55%) and controls (AA: 4%, AG: 47%, GG: 49%) was similar (P=0.594). The allelic frequencies of 3435C>T (ABCB1), -290A>G (CYP3A4) and 6986A>G (CYP3A5) polymorphisms are similar between Chilean HC patients and controls, and comparable to frequencies found in Asian populations.info:eu-repo/semantics/openAccessSociedad Chilena de AnatomíaInternational Journal of Morphology v.29 n.4 20112011-12-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-95022011000400037en10.4067/S0717-95022011000400037
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	Polymorphisms Statins Hypercholesterolemia ABCB1
spellingShingle	Polymorphisms Statins Hypercholesterolemia ABCB1 Rosales,Alexy Pacheco,Alejandro Cuevas,Alejandro Saavedra,Nicolás Zambrano,Tomás Lanas,Fernando Salazar,Luis A Frequency of Common Variants in Genes Involved in Lipid-Lowering Response to Statins in Chilean Subjects with Hypercholesterolemia
description	Interindividual differences in activity and expression of the metabolizing enzymes cytochrome P450 (CYP) 3A4 and 3A5 and the multidrug efflux pump P-glycoprotein (P-gp, encoded by ABCB1 gene) contribute considerably to lipid-lowering efficacy of statin treatment in subjects with hypercholesterolemia. Variability in the activity of CYP3A4, CYP3A5 and P-gp could be considered to result from genetic polymorphisms encoding their genes. However, the available data indicate that the frequencies of ABCB1, CYP3A4 and CYP3A5 gene polymorphisms differ significantly across populations. Thus, the aim of the present study was to determine the allelic frequency of three common variants of these genes in Chilean individuals with primary hypercholesterolemia (HC) and controls. A total of 135 unrelated patients (44 ± 7 years old) with diagnosis of hypercholesterolemia (Total cholesterol 240 mg/dL) and 120 normolipidemic healthy controls (40 ± 10 years old; total cholesterol 200 mg/dL) were included in this study. The 3435C>T (MDR1), -290A>G (CYP3A4) and 6986A>G (CYP3A5) gene polymorphisms were analyzed by PCR-RFLP. The genotype distribution for 3435C>T variant of ABCB1 in HC patients (CC: 49%, CT: 37%, TT: 14%) and controls (CC: 41%, CT: 48%, TT: 11%) was comparable (P=0.186). Similarly, the genotype distribution for -290A>G polymorphism of CYP3A4 in HC subjects (AA: 73%, AG: 27%, GG: 0%) and controls (AA: 71%, AG: 29%, GG: 0%) was equivalent (P = 0.863). Finally, the genotype distribution for 6986A>G variant of CYP3A5 in HC individuals (AA: 4%, AG: 41%, GG: 55%) and controls (AA: 4%, AG: 47%, GG: 49%) was similar (P=0.594). The allelic frequencies of 3435C>T (ABCB1), -290A>G (CYP3A4) and 6986A>G (CYP3A5) polymorphisms are similar between Chilean HC patients and controls, and comparable to frequencies found in Asian populations.
author	Rosales,Alexy Pacheco,Alejandro Cuevas,Alejandro Saavedra,Nicolás Zambrano,Tomás Lanas,Fernando Salazar,Luis A
author_facet	Rosales,Alexy Pacheco,Alejandro Cuevas,Alejandro Saavedra,Nicolás Zambrano,Tomás Lanas,Fernando Salazar,Luis A
author_sort	Rosales,Alexy
title	Frequency of Common Variants in Genes Involved in Lipid-Lowering Response to Statins in Chilean Subjects with Hypercholesterolemia
title_short	Frequency of Common Variants in Genes Involved in Lipid-Lowering Response to Statins in Chilean Subjects with Hypercholesterolemia
title_full	Frequency of Common Variants in Genes Involved in Lipid-Lowering Response to Statins in Chilean Subjects with Hypercholesterolemia
title_fullStr	Frequency of Common Variants in Genes Involved in Lipid-Lowering Response to Statins in Chilean Subjects with Hypercholesterolemia
title_full_unstemmed	Frequency of Common Variants in Genes Involved in Lipid-Lowering Response to Statins in Chilean Subjects with Hypercholesterolemia
title_sort	frequency of common variants in genes involved in lipid-lowering response to statins in chilean subjects with hypercholesterolemia
publisher	Sociedad Chilena de Anatomía
publishDate	2011
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-95022011000400037
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Frequency of Common Variants in Genes Involved in Lipid-Lowering Response to Statins in Chilean Subjects with Hypercholesterolemia

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