Interaction Between NOS3 and HMOX1 on Antihypertensive Drug Responsiveness in Preeclampsia

Rev Bras Ginecol Obstet. 2020 Aug;42(8):460-467. doi: 10.1055/s-0040-1712484. Epub 2020 Jun 19.

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.

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.

MeSH terms

  • Adult
  • Antihypertensive Agents / therapeutic use*
  • Female
  • Heme Oxygenase-1 / genetics*
  • Humans
  • Nitric Oxide Synthase Type III / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Pre-Eclampsia* / drug therapy
  • Pre-Eclampsia* / epidemiology
  • Pre-Eclampsia* / genetics
  • Pregnancy

Substances

  • Antihypertensive Agents
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III
  • HMOX1 protein, human
  • Heme Oxygenase-1