[Association between cytochrome p4502c9 polymorphisms and losartan dosing in hypertensive patients]. / Efecto de las variantes de CYP2C9 sobre la dosis de losartán en hipertensos chilenos.
Rev Med Chil
; 147(12): 1527-1534, 2019 Dec.
Article
em Es
| MEDLINE
| ID: mdl-32186616
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 CYP2C9*2 and CYP2C9*3 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 (CYP2C9*1), 0.05 (CYP2C9*2) and 0.1 (CYP2C9*3). Genotypic frequencies were 73.3% (CYP2C9*1/*1), 6.7% (CYP2C9*1/*2), 16.7% (CYP2C9*1/*3) and 3.3% (CYP2C9*2/3); observing a significantly higher frequency of the allele CYP2C9*3 (p=0.041) and CYP2C9*1/*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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polimorfismo Genético
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Losartan
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Citocromo P-450 CYP2C9
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Hipertensão
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Anti-Hipertensivos
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
País/Região como assunto:
America do sul
/
Chile
Idioma:
Es
Revista:
Rev Med Chil
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Chile
País de publicação:
Chile