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  • blasticidin While increased arginase levels has been shown

    2024-02-23

    While increased arginase levels has been shown in animal models and in humans with cardiovascular dysfunction [16], [22], [23], it is unknown whether plasma levels or activity of Arginase may predict ED risk. In addition, recent evidence suggests that plasma l-arginine hydrolysis by arginases limits the amounts of l-arginine available to promote endothelial NO synthesis [30], even though it is not clear to which extent endothelial blasticidin rely on plasma l-arginine to produce NO. While several studies have shown that genetic variations in genes encoding the components of the NO–cGMP pathway may affect the pathogenesis of ED and therapeutic responses to drugs [2], [8], [12], [13], [31], [32], no previous study has examined whether polymorphisms in the genes encoding Arginase 1 and Arginase 2 (ARG1 and ARG2, respectively) are associated with ED. This study aims at assessing whether plasma levels of Arginase 1 and 2, or Arginase activity, are associated with ED and predict the degree of disability. In addition, this study aims at examining whether those possible associations are influenced by genotypes or haplotypes of ARG1 and ARG2 genes.
    Materials and methods
    Results Clinical features of included subjects are shown in Table 1. Significant between groups differences were found in age, smoking status, systolic blood pressure, and biochemical parameters such as cholesterol and fasting glucose (all P < 0.05). However, the groups were similar with respect to the other parameters shown in Table 1 (P > 0.05). Fig. 1 shows plasma Arginase 1 and Arginase 2 concentrations and Arginase activity in the studied groups. While Arginase 1 and Arginase Activity were not different between groups, higher Arginase 2 levels were found in patients with ED (P = 0.009). Accordingly, multivariate logistic regression analysis (Table 2) showed that Arginase 2 levels are positively associated with ED risk (P = 0.010, OR = 7.9, 95% confidence interval: 1.7 to 39.1), whereas Arginase 1 concentrations and Arginase Activity showed no significant effect. No associations were found between plasma Arginase 1 and 2 levels or plasma Arginase activity and changes in IIEF scores (Supplementary Table 1). Supplementary Table 2 shows the genotypes distributions for ARG1 and ARG2 polymorphisms in the Control and Clinical ED groups. All genotypes frequencies were in Hardy–Weinberg equilibrium. No associations were found between genotypes and disease risk, even after correction for confounding factors. Supplementary Table 3 shows the haplotypes distributions for ARG1 and ARG2 polymorphisms in the Control and Clinical ED groups. Again, no significant association was found between haplotypes and ED after correction for covariates. Interestingly, however, both genotypes and haplotypes were associated with disease severity reflected by alterations in the IIEF score (Table 3, Table 4). While the CC genotype for the rs2781659 polymorphism was associated with reduced IIEF scores in the clinical ED group (B = −7.2, P = 0.006), the variant TT genotype was associated with increased IIEF score (B = +6.9, P = 0.008). Besides, the CC genotype for rs2781667 polymorphism was associated with increased IIEF scores (B = +7.2, P = 0.009), and the variant TT genotype was associated with reduced IIEF scores (B = −6.0, P = 0.021). With respect to haplotypes, the common GTCC haplotype of ARG1 was associated with increased IIEF scores only in the clinical ED group (B = +2.52, P = 0.006). No associations were observed on Control group. We further analyzed which factors could predict plasma arginase activity (Table 5). Interestingly, Arginase 1 and Arginase 2 levels correlated positively with Arginase Activity only in the clinical ED group (B = +0.11, P = 0.043 for Arginase 1 levels, and B = +0.28, P = 0.044 for Arginase 2 levels). Furthermore, we analyzed whether the studied genotypes and haplotypes could predict Arginase 1 and Arginase 2 levels (Supplementary Tables 4 and 5, respectively) and Arginase activity (Supplementary Tables 6 and 7). We found that the rs17599586 polymorphism affects arginase activity only in the clinical ED group (P = 0.031), although specific genotypes effects were not significant (Supplementary Table 6). Other genotypes and haplotypes were not associated with changes in Arginase 1 and Arginase 2 levels, nor with Arginase Activity.