title: Diabetes mellitus and late-onset hypogonadism: the role of Glu298Asp endothelial nitric oxide synthase polymorphism.
abstract: Nitric oxide has been associated with insulin resistance and type 2 diabetes mellitus (DM). An association has been suggested between a single nucleotide polymorphism (Glu298Asp variant) of the endothelial nitric oxide synthase (eNOS) gene and increased risk of DM. However, the role of this polymorphism in favouring DM has not been investigated in hypogonadism, in which low testosterone and obesity are believed to play the major role. We aimed to evaluate whether eNOS gene single nucleotide polymorphism (Glu298Asp variant) might give a relevant contribution also to the onset of hypogonadism-associated DM. 110 men affected by late-onset hypogonadism were retrospectively reviewed. Patients were clinically and biochemically evaluated. Detection of eNOS Glu298Asp polymorphism was performed. After splitting the sample according to the three genetic variants (i.e. eNOSGG , eNOSGT , eNOSTT ), no difference was evident in age, body mass index (BMI) and total testosterone. Conversely, DM prevalence, glycaemia and glycated haemoglobin were significantly higher in eNOSTT than in eNOSGT and eNOSGG . Logistic regression analysis showed that, after adjustment for age, BMI and total testosterone, eNOSTT was positively and significantly associated with DM. Our study suggests that Glu298Asp single nucleotide polymorphism of the eNOS gene may be an independent risk factor for hypogonadism-associated type 2 DM.
authors.affiliation: Andrology Unit, Endocrinology, Department of Clinical and Molecular Sciences, Umberto I Hospital, School of Medicine, Polytechnic University of Marche, Ancona, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Delli Muti
authors.affiliation: Andrology Unit, Endocrinology, Department of Clinical and Molecular Sciences, Umberto I Hospital, School of Medicine, Polytechnic University of Marche, Ancona, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Tirabassi
authors.affiliation: Department of Economy, School of Economy, Polytechnic University of Marche, Ancona, Italy.
authors.forename: G R
authors.initials: GR
authors.lastname: Lamonica
authors.affiliation: Andrology, Pathophysiology of Reproduction and Endocrine Diagnosis Unit, Policlinic Umberto I, University of Rome "La Sapienza", Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Lenzi
authors.affiliation: Andrology Unit, Endocrinology, Department of Clinical and Molecular Sciences, Umberto I Hospital, School of Medicine, Polytechnic University of Marche, Ancona, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Balercia
mesh_terms: D000367:Age Factors; D017668:Age of Onset; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000235:genetics*; D005058:Eunuchism / Q000209:etiology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D013739:Testosterone / Q000097:blood
chemical_list: D013739:Testosterone; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III
keywords: Diabetes mellitus; hypogonadism; nitric oxide synthase; polymorphisms