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

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 tomethyldopa 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.

Keywords:
preeclampsia; polymorphism; antioxidant; nitric oxide