The Association of eNOS G894T Polymorphism with Metabolic Syndrome and Erectile Dysfunction
Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. Journal of Sexual Medicine
(Impact Factor: 3.15).
03/2012; 9(3):837-43. DOI: 10.1111/j.1743-6109.2011.02588.x
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.
Available from: Ebrahim Eskandari-Nasab
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ABSTRACT: Metabolic syndrome (MeS) is associated with increased risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease. There is some evidence indicating that adipokines play a role in the development of MeS. The present study was aimed to investigate the impact of chemerin rs17173608 and vaspin rs2236242 gene polymorphisms with the risk of MeS in a sample of Iranian population. This case-control study was done on 151 subjects with MeS and 149 without MeS, as defined by NCEP-ATPIII. Tetra amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) was designed to detect the polymorphisms. Our finding showed that there are significant differences in genotype frequencies between the groups regarding vaspin rs2236242 polymorphism (χ(2)=18.74, p<0.0001). A significant protection against MeS was found for vaspin rs2236242 in allele and genotypes (Odd Ratio [OR]=0.52; 95% confidence interval [CI]=0.37-0.72; p=0.0001, T vs A; OR=0.49; 95%CI=0.29-0.82; p=0.007, TT vs TA and OR=0.17; 95%CI=0.07-0.40; p<0.0001, TT vs AA). Our finding showed positive association between chemerin rs17173608 polymorphism and risk of MeS (χ(2)=7.70, p=0.021). The G allele increased the risk of MeS (OR=1.78; 95% CI=1.14-2.78; p=0.012) as compared to the T allele. In conclusion, our data suggest for the first time a significant association between vaspin rs2236242 and chemerin rs17173608 polymorphisms and the MeS in Zahedan, southeast Iran. Further studies with large sample size and different ethnicities are required to confirm our findings.
Gene 09/2012; 510(2):113-7. DOI:10.1016/j.gene.2012.08.048 · 2.14 Impact Factor
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ABSTRACT: Previous studies have shown that endothelial nitric oxide synthase (eNOS) gene may be involved in abnormal semen parameters. However, the relationship between eNOS G894T polymorphism and semen parameters remains controversial. The purpose of this study was to investigate the association of eNOS G894T polymorphism and semen parameters. The genotype frequency of eNOS G894T was determined in 270 idiopathic asthenozoospermia patients and 248 ethnically matched healthy volunteers using iPLEX genotyping assays on a MassARRAY(®) (Sequenom, San Diego, CA, USA) platform. The statistical analysis performed with Fisher's exact test showed no significant difference in frequencies of genotypes between both groups. The logistic regression showed that genotypes GT, TT and allele T were nonassociated with increased risk of asthenozoospermia in the patient group with ≤5% or >5% sperm with normal forms. The dependence on genotypes of semen parameters was further investigated in both patients and control group. There was no significant difference as compared to control group (P > 0.05). Our study indicated that eNOS gene G894T polymorphism may not have an adverse effect on semen parameters in a Chinese Han population.
Andrologia 05/2013; 46(5). DOI:10.1111/and.12113 · 1.63 Impact Factor
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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; 10(9). DOI:10.1111/jsm.12245 · 3.15 Impact Factor
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