Efecto de las variantes de CYP2C9 sobre la dosis de losartán en hipertensos chilenos

Background Losartan is widely used in many clinicals settings. Its dosage is related to the genetic characteristics of CYP2C9 enzymatic activity, which metabolizes losartan to its active form E-3174, responsible for the antihypertensive effect. Aims To identify the frequency of allelic variants CY...

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Autores principales:	PEDREROS-ROSALES,CRISTIAN, JALIL MILAD,ROBERTO, LAGOS LUCERO,MARCELA, SOLARI GAJARDO,SANDRA
Lenguaje:	Spanish / Castilian
Publicado:	Sociedad Médica de Santiago 2019
Materias:	Cytochrome P-450 CYP2C9 Genotype Losartan Polimorphism, Genetic
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0034-98872019001201527
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spelling	oai:scielo:S0034-988720190012015272020-07-22Efecto de las variantes de CYP2C9 sobre la dosis de losartán en hipertensos chilenosPEDREROS-ROSALES,CRISTIANJALIL MILAD,ROBERTOLAGOS LUCERO,MARCELASOLARI GAJARDO,SANDRA Cytochrome P-450 CYP2C9 Genotype Losartan Polimorphism, Genetic Background Losartan is widely used in many clinicals settings. Its dosage is related to the genetic characteristics of CYP2C9 enzymatic activity, which metabolizes losartan to its active form E-3174, responsible for the antihypertensive effect. Aims To identify the frequency of allelic variants CYP2C92 and CYP2C93 in hypertensive patients and to compare genotypes with a healthy Chilean population. To relate polymorphisms with the losartan dosing to obtain an optimal blood pressure. Material and Methods We studied 30 patients with controlled essential hypertension using losartan with normal liver function, and 202 healthy people. Peripheral blood DNA genotyping was performed by polymerase chain reaction to identify the polymorphisms. Allelic and genotypic frequencies were compared. Results In hypertensive patients, allelic frequencies were 0.85 (CYP2C91), 0.05 (CYP2C92) and 0.1 (CYP2C93). Genotypic frequencies were 73.3% (CYP2C91/1), 6.7% (CYP2C91/2), 16.7% (CYP2C91/3) and 3.3% (CYP2C92/3); observing a significantly higher frequency of the allele CYP2C93 (p=0.041) and CYP2C91/3 genotype (p=0.04). A non-significant tendency to need a larger dose of losartan was observed with the CYP2C9 3 allele, with an odds ratio (OR) of 1.46 (95% confidence intervals (CI) 0.01-18.64). The same tendency was observed with the need to use losartan twice a day, obtaining an OR of 5.88 (CI 0.54 -62.14). Conclusions There could be a relationship between the presence of CYP2C9 polymorphisms and the pathogenesis of hypertension. The presence of CYP2C9*3 is associated with the need for higher doses of losartan, possibly due to a decrease in the conversion of losartan to E-3174.info:eu-repo/semantics/openAccessSociedad Médica de SantiagoRevista médica de Chile v.147 n.12 20192019-12-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0034-98872019001201527es10.4067/S0034-98872019001201527
institution	Scielo Chile
collection	Scielo Chile
language	Spanish / Castilian
topic	Cytochrome P-450 CYP2C9 Genotype Losartan Polimorphism, Genetic
spellingShingle	Cytochrome P-450 CYP2C9 Genotype Losartan Polimorphism, Genetic PEDREROS-ROSALES,CRISTIAN JALIL MILAD,ROBERTO LAGOS LUCERO,MARCELA SOLARI GAJARDO,SANDRA Efecto de las variantes de CYP2C9 sobre la dosis de losartán en hipertensos chilenos
description	Background Losartan is widely used in many clinicals settings. Its dosage is related to the genetic characteristics of CYP2C9 enzymatic activity, which metabolizes losartan to its active form E-3174, responsible for the antihypertensive effect. Aims To identify the frequency of allelic variants CYP2C92 and CYP2C93 in hypertensive patients and to compare genotypes with a healthy Chilean population. To relate polymorphisms with the losartan dosing to obtain an optimal blood pressure. Material and Methods We studied 30 patients with controlled essential hypertension using losartan with normal liver function, and 202 healthy people. Peripheral blood DNA genotyping was performed by polymerase chain reaction to identify the polymorphisms. Allelic and genotypic frequencies were compared. Results In hypertensive patients, allelic frequencies were 0.85 (CYP2C91), 0.05 (CYP2C92) and 0.1 (CYP2C93). Genotypic frequencies were 73.3% (CYP2C91/1), 6.7% (CYP2C91/2), 16.7% (CYP2C91/3) and 3.3% (CYP2C92/3); observing a significantly higher frequency of the allele CYP2C93 (p=0.041) and CYP2C91/3 genotype (p=0.04). A non-significant tendency to need a larger dose of losartan was observed with the CYP2C9 3 allele, with an odds ratio (OR) of 1.46 (95% confidence intervals (CI) 0.01-18.64). The same tendency was observed with the need to use losartan twice a day, obtaining an OR of 5.88 (CI 0.54 -62.14). Conclusions There could be a relationship between the presence of CYP2C9 polymorphisms and the pathogenesis of hypertension. The presence of CYP2C9*3 is associated with the need for higher doses of losartan, possibly due to a decrease in the conversion of losartan to E-3174.
author	PEDREROS-ROSALES,CRISTIAN JALIL MILAD,ROBERTO LAGOS LUCERO,MARCELA SOLARI GAJARDO,SANDRA
author_facet	PEDREROS-ROSALES,CRISTIAN JALIL MILAD,ROBERTO LAGOS LUCERO,MARCELA SOLARI GAJARDO,SANDRA
author_sort	PEDREROS-ROSALES,CRISTIAN
title	Efecto de las variantes de CYP2C9 sobre la dosis de losartán en hipertensos chilenos
title_short	Efecto de las variantes de CYP2C9 sobre la dosis de losartán en hipertensos chilenos
title_full	Efecto de las variantes de CYP2C9 sobre la dosis de losartán en hipertensos chilenos
title_fullStr	Efecto de las variantes de CYP2C9 sobre la dosis de losartán en hipertensos chilenos
title_full_unstemmed	Efecto de las variantes de CYP2C9 sobre la dosis de losartán en hipertensos chilenos
title_sort	efecto de las variantes de cyp2c9 sobre la dosis de losartán en hipertensos chilenos
publisher	Sociedad Médica de Santiago
publishDate	2019
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0034-98872019001201527
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Efecto de las variantes de CYP2C9 sobre la dosis de losartán en hipertensos chilenos

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