ARG2 single-nucleotide polymorphism rs3742879 affects plasma arginase 2 levels, nitric oxide formation and antihypertensive therapy response in preeclampsia

Author:

Luizon Marcelo R1ORCID,Pinto-Souza Caroline C2,Coeli-Lacchini Fernanda3,Lacchini Riccardo4,Cavalli Ricardo C5,Sandrim Valeria C2ORCID

Affiliation:

1. Department of Genetics, Ecology & Evolution, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, 31270-901, Brazil

2. Department of Biophysics & Pharmacology, Institute of Biosciences of Botucatu, Universidade Estadual Paulista (UNESP), Distrito Rubiao Junior, Botucatu, Sao Paulo, 18618-689, Brazil

3. Department of Clinical Analyses, Toxicology & Food Science, School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo (USP), Ribeirao Preto, Sao Paulo, 14040-903, Brazil

4. Department of Psychiatric Nursing & Human Sciences, Ribeirao Preto School of Nursing, University of Sao Paulo (USP), Ribeirao Preto, Sao Paulo, 14049-900, Brazil

5. Department of Gynecology & Obstetrics, University of Sao Paulo (USP), Ribeirao Preto, Sao Paulo, 14049-900, Brazil

Abstract

Aim: This work examined whether ARG1 (rs2781659, rs2781667, rs2246012 and rs17599586) and ARG2 (rs3742879 and rs10483801) single-nucleotide polymorphisms (SNPs) are associated with antihypertensive therapy responsiveness in preeclampsia (PE) and their effects on arginase isoforms and nitrite concentrations in responsive and nonresponsive patients. Methods: SNP genotypes were determined by TaqMan assays. Plasma arginase levels were measured by ELISA and nitrite concentrations were measured using an ozone-based chemiluminescence assay. Results: The G allele for ARG2 rs3742879 (A>G) was less frequent in nonresponsive compared with responsive patients (15.5% vs 24.7%, respectively) and the G carriers of the nonresponsive subgroup had lower arginase 2 (9.2 ± 7.5 ng/ml vs 19.1 ± 17.3 ng/ml) and higher nitrite concentrations (110.2 ± 52.8 nM vs 78.5 ± 37.9 nM) than carriers of the AA genotype (all p < 0.05). Conclusion: ARG2 SNP rs3742879 is associated with diminished arginase 2 levels and increased nitric oxide formation in nonresponsive PE patients.

Funder

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Fundação de Amparo à Pesquisa do Estado de São Paulo

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

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