Relationship between asymmetric dimethylarginine, nitrite and genetic polymorphisms: Impact on erectile dysfunction therapy

Author(s):Show less -

Milanez Azevedo, Ana Maria ^[1] ; Brites-Anselmi, Guilhermo ^[2] ; Pinheiro, Lucas Cezar ^[1] ; Belo, Vanessa de Almeida ^[3] ; Coeli-Lacchini, Fernanda Borchers ^[4] ; Fernandes Molina, Carlos Augusto ^[5] ; de Andrade, Murilo Ferreira ^[5] ; Tucci, Jr., Silvio ^[5] ; Hirsch, Emilio ^[6] ; Tanus-Santos, Jose Eduardo ^[1] ; Lacchini, Riccardo ^[2]

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Coll Nursing, Dept Psychiat Nursing & Human Sci, Ribeirao Preto, SP - Brazil

^[3] Univ Fed Minas Gerais, Biol Sci Inst, Dept Gen Biol, Belo Horizonte, MG - Brazil

^[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Internal Med, Ribeirao Preto, SP - Brazil

^[5] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Surg & Anat, Ribeirao Preto, SP - Brazil

^[6] Univ Turin, Dept Mol Biotechnol & Hlth Sci, Turin - Italy

• Document type: Journal article
• Source: NITRIC OXIDE-BIOLOGY AND CHEMISTRY; v. 71, p. 44-51, DEC 1 2017.
• Web of Science Citations: 1

Abstract

Sildenafil is the most used treatment of erectile dysfunction, however a large part of patients do not respond to therapy. This drug enhances nitric oxide (NO) signaling, and therefore factors that alter NO production may impact this drug responsiveness. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of all NO synthases, and is metabolized by Dimethylarginine Dimethilaminohydrolase (DDAH) 1 and 2. Here we aimed to assess the relationship between plasma levels of ADMA and nitrite (marker of nitric oxide production) with Sildenafil responsiveness. We also studied generic polymorphisms in DDAH1 and DDAH2 genes and their relation with biochemical and clinical data. Were included here 140 patients, divided in Clinical Erectile Dysfunction (CED) or Post-Prostatectomy Erectile Dysfunction (PPED) groups. Erectile function was evaluated before and after Sildenafil on-demand treatment using the International Index for Erectile Function Questionnaire. We have found that nitrite was associated with worse response to Sildenafil (r = - 0.25, P = 0.040). rs1554597 and rs18582 DDAH1 polymorphisms were associated with changes in ADMA levels in CED (B = - 0.23, P = 0.002; B = - 0.15, P = 0.017 for both variant genotypes, respectively). Finally, DDAH2 polymorphisms were associated with altered responsiveness to Sildenafil in PPED (B = +0.19, P = 0.027). (AU)

• FAPESP's process: 16/04449-0 - Genetics of erectile dysfunction: asymetrical dimethylarginine related genes affecting sildenafil responsiveness
• Grantee: Riccardo Lacchini
• Support Opportunities: Regular Research Grants