Relationship between Arginase 1 and Arginase 2 levels and genetic polymorphisms with erectile dysfunction

• Nitric oxide is an essential part of the physiology of erectile function.
• Arginase 1 and 2 compete for l-arginine with all nitric oxide synthases.
• Arginase 1 and 2 inhibition improve erectile function in animals.
• We found higher Plasma Arginase 2 levels in erectile dysfunction (ED) patients.
• We found an association of polymorphisms in ARG1 with the degree of disability in ED.

Arginase 1 and Arginase 2 are homologous enzymes that convert l-Arginine to Urea and l-ornithine and compete with nitric oxide synthases for l-Arginine. Increased Arginase 1 and 2 activity may reduce nitric oxide production by the endothelium in disease states, including erectile dysfunction (ED). Here we aimed at assessing whether Arginase 1 and 2 plasma levels, plasma arginase activity, or genetic factors are associated with ED risk and severity. Blood samples were collected from healthy controls (n = 106) and from patients with ED (n = 110) after completion of the IIEF questionnaire (international index of erectile function). Plasma Arginase 1 and 2 concentrations were assessed by ELISA, while plasma arginase activity was measured by spectrophotometry. Genotypes of ARG1 (rs2781659, rs2781667, rs2246012 and rs17599586) and ARG2 (rs3742879 and rs10483801) were determined by Taqman genotyping assays by real-time polymerase chain reaction. Increased Arginase 2 concentrations were found in clinical ED and are associated with increased risk for ED. ARG1 rs2781659 AA and rs2781667 TT genotypes are associated with lower IIEF scores (higher severity) only in clinical ED. Similarly, the ARG1 GTCC haplotype is associated with higher IIEF scores in clinical ED. This study shows that plasma Arginase 2 concentrations may serve as risk factor for ED. Besides, Arginase 1 genetic variations affect ED severity.