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CC BY 4.0 · Rev Bras Ginecol Obstet 2020; 42(08): 460-467
DOI: 10.1055/s-0040-1712484
Original Article
Obstetrics/High Risk Pregnancy

Interaction Between NOS3 and HMOX1 on Antihypertensive Drug Responsiveness in Preeclampsia

Interação entre os genes NOS3 e HMOX1 na resposta à terapia antihipertensiva em pré-eclâmpsia
Valeria Cristina Sandrim 
1   Department of Pharmacology, Instituto de Biociências de Botucatu da Universidade Estadual Paulista, Botucatu, SP, Brazil
,
Marcelo Rizzatti Luizon 
2   Department of Genetics, Ecology and Evolution, Instituto de Ciências Biológicas da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
,
Eliane Pilan 
1   Department of Pharmacology, Instituto de Biociências de Botucatu da Universidade Estadual Paulista, Botucatu, SP, Brazil
,
Mayara Caldeira-Dias 
1   Department of Pharmacology, Instituto de Biociências de Botucatu da Universidade Estadual Paulista, Botucatu, SP, Brazil
,
Fernanda Borchers Coeli-Lacchini 
3   Department of Internal Medicine, Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, São Paulo, SP, Brazil
,
Georgia Kors 
1   Department of Pharmacology, Instituto de Biociências de Botucatu da Universidade Estadual Paulista, Botucatu, SP, Brazil
,
Iuly Berndt 
1   Department of Pharmacology, Instituto de Biociências de Botucatu da Universidade Estadual Paulista, Botucatu, SP, Brazil
,
Riccardo Lacchini 
4   Department of Psychiatric Nursing and Human Sciences, Escola de Enfermagem de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
,
Ricardo Carvalho Cavalli 
5   Department of Gynecology and Obstetrics, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
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Abstract

Objective We examined the interaction of polymorphisms in the genes heme oxygenase-1 (HMOX1) and nitric oxide synthase (NOS3) in patients with preeclampsia (PE) as well as the responsiveness to methyldopa and to total antihypertensive therapy.

Methods The genes HMOX1 (rs2071746, A/T) and NOS3 (rs1799983, G/T) were genotyped using TaqMan allele discrimination assays (Applied Biosystems, Foster City, CA, USA ), and the levels of enzyme heme oxygenase-1 (HO-1) were measured using enzyme-linked immunosorbent assay (ELISA).

Results We found interactions between genotypes of the HMOX-1 and NOS3 genes and responsiveness to methyldopa and that PE genotyped as AT presents lower levels of protein HO-1 compared with AA.

Conclusion We found interactions between the HMOX-1 and NOS3 genes and responsiveness to methyldopa and that the HMOX1 polymorphism affects the levels of enzyme HO-1 in responsiveness to methyldopa and to total antihypertensive therapy. These data suggest impact of the combination of these two polymorphisms on antihypertensive responsiveness in PE.

Resumo

Objetivo Examinamos a interação dos polimorfismos nos genes heme oxigenase-1 (HMOX1) eóxido nítrico sintase (NOS3) em pacientes com pré-eclâmpsia (PE)bem como as capacidades de resposta à metildopa e à terapia anti-hipertensiva.

Métodos Os polimorfismos nos genes HMOX1 (rs2071746, A/T) e NOS3 (rs1799983, G/T) foram genotipados usando TaqMan allele discrimination assays (Applied Biosystems, Foster City, CA, EUA), e os níveis da enzima heme oxigenase-1 (HO-1) foram medidos por enzyme-linked immunosorbent assay (ELISA).

Resultados Foram encontradas interações entre os genótipos da HMOX-1 e NOS3 e responsividade à metildopa, e que pacientes genotipados como AT apresentam níveis mais baixos de proteína HO-1 em comparação com o genótipo AA.

Conclusão Foram encontradas interações entre os genes HMOX-1 e NOS3 e responsividade à metildopa e que o polimorfismo localizado no gene HMOX1 afeta os níveis de enzima HO-1 na resposta à metildopa e à terapia anti-hipertensiva. Esses dados sugerem o impacto da combinação desses dois polimorfismos na resposta anti-hipertensiva na PE.

Keywords

preeclampsia - polymorphism - antioxidant - nitric oxide

Palavras-chave

pré-eclâmpsia - polimorfismo - antioxidante - óxido nítrico

Contributions

Sandrim VC participated in the genetic analysis, study design, was involved in the statistical analyses and in the manuscript writing. Pilan E., Caldeira-Dias M., Coeli-Lacchini F. B., Kors G., Berndt I., Lacchini R., Luizon M. R. participated in the genetic analysis, and manuscript writing and revision. Cavalli R. C. participated in the study by recruiting the patients, collecting the samples, and revising the manuscript.


Supplementary Material



Publication History

Received: 22 January 2020

Accepted: 30 March 2020

Article published online:
19 June 2020

© 2020. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).

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Rio de Janeiro, Brazil

 

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