title: Influence of arginase polymorphisms and arginase levels/activity on the response to erectile dysfunction therapy with sildenafil.
abstract: Arginase 1 (ARG1) and arginase 2 (ARG2) compete with nitric oxide synthases for the substrate l-arginine. Here we aim to assess whether arginase 1 and 2 plasma levels, plasma arginase activity or genetic factors are associated with altered responsiveness to sildenafil. We studied 71 post-prostatectomy erectile dysfunction (ED) patients (PED group) and 72 clinical ED patients (CED). Patients responded to the International Index of Erectile Function questionnaire before and after the treatment. We found positive and negative correlations between plasma levels of arginase 1 and sildenafil responsiveness in the PED and CED groups, respectively. PED group also presented negative correlation between plasma arginase activity and sildenafil responsiveness. Sildenafil poor responders have shown higher plasma arginase activity in PED and higher arginase 1 levels on CED groups. In addition, variant genotypes for the rs2781659, rs2781667 and rs17599586 polymorphisms were associated with reduced arginase activity, as well as the GTTT ARG1 haplotype in CED group.
authors.affiliation: Department of Psychiatric Nursing and Human Sciences, Ribeirao Preto College of Nursing, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: R
authors.initials: R
authors.lastname: Lacchini
authors.affiliation: Department of Psychiatric Nursing and Human Sciences, Ribeirao Preto College of Nursing, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: J J
authors.initials: JJ
authors.lastname: Muniz
authors.affiliation: Department of Surgery and Anatomy, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: Y T D A
authors.initials: YTDA
authors.lastname: Nobre
authors.affiliation: Department of Surgery and Anatomy, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: A J
authors.initials: AJ
authors.lastname: Cologna
authors.affiliation: Department of Surgery and Anatomy, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: A C P
authors.initials: ACP
authors.lastname: Martins
authors.affiliation: Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: J E
authors.initials: JE
authors.lastname: Tanus-Santos
mesh_terms: D000328:Adult; D000368:Aged; D001119:Arginase / Q000037:antagonists & inhibitors / Q000097:blood* / Q000235:genetics*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D007172:Erectile Dysfunction / Q000097:blood* / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D000068677:Sildenafil Citrate / Q000097:blood* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000097:blood* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; C574619:ARG1 protein, human; D001119:Arginase