DDAH1 and DDAH2 polymorphisms associate with asymmetrical dimethylarginine plasma levels in erectile dysfunction patients but not in healthy controls

• Published in: Nitric oxide Vol. 92; pp. 11 - 17
• Main Authors: Brites-Anselmi, Guilhermo, Azevedo, Ana Maria Milanez, Miyazaki, Anderson Heiji Lima, Pinheiro, Lucas Cezar, Coeli-Lacchini, Fernanda Borchers, de Andrade, Murilo Ferreira, Molina, Carlos Augusto Fernandes, Tucci, Silvio, Hirsch, Emilio, Tanus-Santos, Jose Eduardo, Lacchini, Riccardo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-11-2019
• Subjects: Adult; Aged; Aged, 80 and over; Amidohydrolases - antagonists & inhibitors; Amidohydrolases - genetics; Amidohydrolases - metabolism; Arginine - analogs & derivatives; Arginine - blood; Arginine - pharmacology; Asymmetrical dimethylarginine; DDAH1; DDAH2; Erectile dysfunction; Erectile Dysfunction - blood; Erectile Dysfunction - enzymology; Female; Genetic polymorphisms; Humans; Male; Middle Aged; Nitric oxide; Nitric Oxide - biosynthesis; Polymorphism, Genetic - genetics; Erectile dysfunction; Asymmetrical dimethylarginine; DDAH1; DDAH2; Nitric oxide; Genetic polymorphisms
• ISSN: 1089-8603; 1089-8611
• DOI: 10.1016/j.niox.2019.08.001

Erectile Dysfunction (ED) is one of the main complaints of aging male. A reduced production of Nitric Oxide (NO) may be involved in ED pathogenesis. NO is synthesized from l-Arginine, and asymmetrical dimethylarginine inhibits all NO synthases. DDAH1 and DDAH2 are genes that encode enzymes responsible for metabolizing ADMA. We aimed to assess whether: 1) ADMA and nitrite levels associated with ED risk and with symptoms intensity; and whether 2) DDAH1 and DDAH2 gene polymorphisms associate with changes in biochemical data, and with ED risk and symptoms intensity. In this study were included 98 healthy controls and 130 ED patients. ADMA levels were measured by ELISA and nitrite levels by Chemiluminescence. DDAH1 and DDAH2 polymorphisms were assessed by Taqman assays. We found that ED had increased nitrite levels and lower ADMA levels than Control group (P < 0.05). We found a significant correlation of ADMA with Nitrite levels only in ED (B = -0.57, P < 0.001). Genotypes and haplotypes of DDAH1 were associated with ADMA levels in ED (P < 0.05), while haplotypes of DDAH2 were associated with levels of nitrite in ED (P < 0.05). Erectile dysfunction patients show an association between DDAH1 and DDAH2 polymorphisms with ADMA levels, which in turn are negatively correlated with nitrite levels. This is not evident on healthy controls.
•ADMA and nitrite plasma levels are negatively associated when ED is present.•There is no association between ADMA and nitrite in healthy controls.•Nitrite levels correlate negatively with Erectile function.•DDAH1 and DDAH2 polymorphisms were associated with changes in ADMA and Nitrite levels.•DDAH1 and DDAH2 polymorphisms were not associated with changes in erectile function, nor ED risk.