The association of eNOS G894T polymorphism with metabolic syndrome and erectile dysfunction.
ABSTRACT Accumulated evidences have outlined the potential relation between insulin resistance and endothelial dysfunction. The impaired ability of endothelium to synthesize or release nitric oxide may provide a common pathophysiological mechanism in the development of metabolic syndrome (MtS) and erectile dysfunction (ED).
The aim of this article was to investigate the genetic susceptibility of endothelial nitric oxide synthase (eNOS) G894T polymorphism underlying the development of both disorders.
A total of 590 subjects with a mean (standard deviation) age of 55.3 years (4.1) were enrolled during a free health screening. Complete clinical data and questionnaires were taken for all subjects. Multivariate logistic regression analysis was used to determine the independent predictors of MtS and ED. The eNOS G894T polymorphism was determined using a polymerase chain reaction-restriction fragment length polymorphism method.
The definition of MtS was according to the modified criteria developed by the Bureau of Health Promotion in Taiwan. Patients with ED were defined as those having a five-item International Index of Erectile Function (IIEF-5) <21.
Our results showed that the eNOS 894T allele carriers had significantly higher prevalence of MtS and ED (odds ratio [OR]=1.64, 95% confidence interval [CI]=1.05∼2.56, P=0.02 and OR=1.76, 95% CI=1.11∼2.80, P=0.01, respectively) after adjustment for each other and age. Also the T allele carriers had significantly lower IIEF-5 score and more MtS components than G allele carriers (P<0.01 and P<0.01, respectively), which were significantly associated with an increment of the T allele number (P<0.05).
The eNOS 894T allele carriers are at greater risk for both MtS and ED, suggesting that eNOS G894T gene polymorphism might play an implication as a common genetic susceptibility factor to develop both disorders.
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ABSTRACT: Increased angiotensin II (AngII) levels cause hypertension, which is a major risk factor for erectile dysfunction (ED). Studies have demonstrated that increased AngII levels in penile tissue are associated with ED. A recent study showed that metformin treatment restored nitric oxide synthase (NOS) protein expression in penile tissue in obese rats; however, whether metformin treatment can be beneficial and restore erectile function in a model of ED has not yet been established. The goal of this study was to test the hypothesis that AngII induces ED by means of increased corpus cavernosum contraction, and that metformin treatment will reverse ED in AngII-treated rats. Male Sprague-Dawley rats were implanted with mini-osmotic pumps containing saline or AngII (70 ng/minute, 28 days). Animals were then treated with metformin or vehicle during the last week of AngII infusion. Intracavernosal pressure; corpus cavernosum contraction and relaxation; nNOS protein expression; extracellular signal-regulated kinase (ERK1/2), AMP-activated protein kinase (AMPK), and eNOS protein expression and phosphorylation. AngII-induced ED was accompanied with an increase in corpus cavernosum contractility, decreased nitrergic relaxation, and increased ERK1/2 phosphorylation. Metformin treatment improved erectile function in the AngII-treated rats by reversing the increased contraction and decreased relaxation. Metformin treatment also resulted in an increase in eNOS phosphorylation at ser1177. Metformin treatment increased eNOS phosphorylation and improved erectile function in AngII hypertensive rats by reestablishing normal cavernosal smooth muscle tone. Labazi H, Wynne BM, Tostes R, and Webb RC. Metformin treatment improves erectile function in an angiotensin II model of erectile dysfunction. J Sex Med **;**:**-**.Journal of Sexual Medicine 07/2013; · 3.15 Impact Factor
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ABSTRACT: IntroductionSeveral studies have linked the association between lower urinary tract symptoms (LUTS), erectile dysfunction (ED), and the presence of insulin resistance (IR) due to an underlined metabolic syndrome (MetS).AimThis study aims to determine the relationship between IR, sexual function, and LUTS and to demonstrate the ability of IR in predicting ED and severe LUTS.Methods Between January 2008 to January 2013, 544 consecutive patients with benign prostatic hyperplasia-related LUTS were enrolled. LUTS and sexual function of the patients were evaluated by the International Index of Erectile Function (IIEF) and the International Prostate Symptom Score (IPSS). MetS was defined by the International Diabetes Federation. IR was defined as a homeostasis model assessment (HOMA) index of 3 or greater.Main Outcome MeasuresUni- and multivariate logistic regression analysis was performed to assess significant predictors of severe LUTS (IPSS ≥20) and ED (IIEF-Erectile Function [IIEF-EF] <26), including MetS component, prostate volume, prostate-specific antigen, total testosterone, and HOMA index.ResultsIR patients resulted in higher values of IPSS (19.0 vs. 15.0; P < 0.01), IPSS-storage (6.0 vs. 5.0; P < 0.01), IPSS-voiding (12.0 vs. 9.0; P < 0.01), total prostate volume (54.8 vs. 36.5; P < 0.01), and lower values of IIEF-EF (17.0 vs. 20.0; P < 0.01), IIEF-Intercourse Satisfaction (3.0 vs. 10.0; P < 0.01), IIEF-Orgasmic Function (8.0 vs. 9.0; P < 0.01), IIEF-Overall Satisfaction (6.0 vs. 8.0; P < 0.01), and total testosterone (3.83 vs. 4.44; P < 0.01). IR was demonstrated to be a strong predictor of ED (IIEF-EF <26) (odds ratio [OR] = 6.20, P < 0.01) after adjusting for confounding factors. Finally, IR was also an independent predictor of severe LUTS (IPSS ≥20) (OR = 2.0, P < 0.01) after adjusting for confounding factors.ConclusionsIR patients are at high risk of having severe LUTS and contemporary sexual dysfunctions. We strongly suggest to prevent LUTS and ED by reducing insulin resistance. Russo GI, Cimino S, Fragalà E, Privitera S, La Vignera S, Condorelli R, Calogero AE, Castelli T, Favilla V, and Morgia G. Insulin resistance is an independent predictor of severe lower urinary tract symptoms and of erectile dysfunction: Results from a cross-sectional study. J Sex Med **;**:**–**.Journal of Sexual Medicine 06/2014; · 3.15 Impact Factor
- International Journal of Bioinformatics Research and Applications 01/2014;