ARG2 Single-Nucleotide Polymorphism RS3742879 Affects Plasma Arginase 2 Levels, Nitric Oxide Formation and Antihypertensive Therapy Response in Preeclampsia

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.

Keywords::

• ARG2
• arginase 2
• genetic polymorphisms
• hypertension
• nitric oxide
• nitrite
• pharmacogenetics
• preeclampsia

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/pgs-2022-0079

Author contributions

CC Pinto-Souza, VC Sandrim, F Coeli-Lacchini, R Lacchini, RC Cavalli and MR Luizon made substantial contributions to the conception or design of the work and acquisition, analysis or interpretation of data. CC Pinto-Souza, VC Sandrim, F Coeli-Lacchini, R Lacchini, RC Cavalli and MR Luizon wrote the research or critically reviewed it for relevant intellectual content and approved the final version to be published. All authors have agreed to be responsible for all aspects of the work to ensure that issues relating to the accuracy or completeness of any part of it are properly investigated and resolved.

Financial & competing interests disclosure

This work was supported by the National Council for Scientific and Technological Development (CNPq/Brazil, grant no. 2014-5/305587 and 308504/2021-6), the Sao Paulo Research Foundation (FAPESP/Brazil, grant no. 2019/07230-8) and Coordination for the Improvement of Higher-Level Personnel (CAPES/Brazil, grant no. financial code 001). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained approval from The Research Ethics Committee of the Faculty of Medicine of Ribeirao Preto, University of Sao Paulo (FMRP-USP) for all human investigations, which were consecutively enrolled in the Department of Gynecology and Obstetrics of the University Hospital of FMRP-USP. In addition, informed consent was obtained from the participants involved.

Additional information

Funding

This work was supported by the National Council for Scientific and Technological Development (CNPq/Brazil, grant no. 2014-5/305587 and 308504/2021-6), the Sao Paulo Research Foundation (FAPESP/Brazil, grant no. 2019/07230-8) and Coordination for the Improvement of Higher-Level Personnel (CAPES/Brazil, grant no. financial code 001). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript.