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We found a protective effect of the GTCC haplotype
We found a protective effect of the GTCC haplotype against ED, which is reflected by its association with increased IIEF in patients with clinical ED. Further studies are required to determine the functional implications of these genetic markers combined in specific haplotypes blocks. Indeed, we found no significant effects of the studied polymorphisms on Arginase1 and Arginase 2 Adapalene sodium salt synthesis concentrations (Supplementary Tables 4 and 5). However, the ARG1 rs17599586 polymorphism seems to affect arginase activity (P = 0.031, Supplementary Table 6). While this last result shows limited effects for this polymorphism, molecular mechanisms remain to be determined.
As strengths of the present study, we should take into consideration the evaluation of healthy controls (without comorbidities; those with IIEF score <21 were excluded from our study) and patients, the vasculogenic-enriched clinical ED group, and the fact that we have covered the most common haplotypes blocks for ARG1. As limitations, we should mention the relatively low number of patients to assess disease susceptibility, which is robust for the biochemical analysis we performed. Nevertheless, power analysis calculation using PGA software [47] showed statistical power above 80% to detect a 2.28 odds ratio in the association with ED. Another limitation of this study is that we have evaluated polymorphisms that do not have a clear functional effect described yet. This makes it more difficult to establish a causative role for the studied polymorphisms, and may explain why there are some inconsistencies between associations we show here with what would be expected from previously reported clinical data. Further studies on this gene are needed to identify the individual functional effect of each of the studied polymorphisms individually and the effect of them when combined in haplotypes.
Conclusions
Circulating Arginase 2 concentrations increase in clinical ED and are associated with increased risk for ED, and therefore may be a useful biomarker for ED. Moreover, ARG1 rs2781659 AA and rs2781667 TT genotypes were associated with lower IIEF scores (increased severity) in clinical ED, whereas ARG1 GTCC haplotype is associated with higher IIEF scores in clinical ED, thus suggesting a genetic contribution of ARG1 variations to ED.
Conflict of interest
Acknowledgments
This study was supported by Fundação de Amparo à Pesquisa do Estado de Sao Paulo (FAPESP – Grant 2013/13346-2) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).
Introduction
Arginases catalyze the hydrolysis of arginine to ornithine and urea and exist in two isoforms: arginases 1 and 2 (Yu et al., 2001). Arginase 1, which is a hepatic arginase, and arginase 2, which is an extrahepatic arginase, are differentially expressed in various tissues of the rat and mouse based on RT-PCR, in situ hybridization, and immunohistochemistry (Choi et al., 2012, Nakamura et al., 1999, Yu et al., 2001).
Recent studies have reported that the main olfactory system in ungulates is deeply involved in maternal (Keller and Levy, 2012, Kendrick et al., 1992), reproductive-sexual (Baum and Cherry, 2015), social (Keller and Levy, 2012, Sanchez-Andrade and Kendrick, 2009, Villagran and Ungerfeld, 2013), and fear-related (Osada et al., 2014) behaviors. The Korean roe deer, Capreolus pygargus, is an ungulate and is the most abundant wild animal on Jeju Island, South Korea. Previously, we reported the morphological characteristics of the vomeronasal system (Park et al., 2014), chemosensory olfactory mucosae (Park et al., 2015), and γ-amino butyric acid (GABA) transmission in the main olfactory bulb (MOB) (Kim et al., 2015). However, little is known about arginase in the main olfactory system of wild ungulates, including roe deer. In this study, we examined the distribution of arginases 1 and 2 in the olfactory bulbs (OB) of C. pygargus by immunohistochemistry.