title: Intron 4 a/b polymorphism of the endothelial nitric oxide synthase gene is associated with both type 1 and type 2 diabetes in a genetically homogeneous population.
abstract: Current classifications of diabetes distinguish between type 1 diabetes (T1D) and type 2 diabetes (T2D), however recent evidence highlights overlap between T1D and T2D. Earlier studies have suggested altered nitric oxide (NO) metabolism in both T1D and T2D. In the present case-control study, we investigated whether the endothelial NO synthase gene intron 4 a/b polymorphism is associated with T1D and T2D in the island of Crete, a well-defined area with genetically homogeneous population. Mutated allele "a" was more common in individuals with both T1D and T2D than in controls (odds ratio [OR] = 1.71, 95% confidence interval [CI] = 1.06-2.77, p = 0.013; and OR = 1.50, 95% CI = 0.930-2.42, p = 0.047, respectively). Mutated genotype (a/a or a/b) was more common in individuals with T1D than in nondiabetic individuals (OR = 1.93, 95% CI = 1.12-3.32, p = 0.008); this increased frequency was also observed for T2D, although not at a significant level (OR = 1.38, 95% CI = 0.802-2.37). No difference was found in the frequency of mutated allele a or mutated genotype (a/a or a/b) between T1D and T2D populations. In conclusion, our results indicate that allele a of the intron 4 endothelial NO synthase gene is associated with susceptibility to both T1D and T2D and may represent a common genetic factor for diabetes.
authors.affiliation: Department of Paediatrics, University of Crete, Heraklion, Crete, Greece.
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Galanakis
authors.forename: Diamantis
authors.initials: D
authors.lastname: Kofteridis
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Stratigi
authors.forename: Eleni
authors.initials: E
authors.lastname: Petraki
authors.forename: Vassilios
authors.initials: V
authors.lastname: Vazgiourakis
authors.forename: Eleni
authors.initials: E
authors.lastname: Fragouli
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Mamoulakis
authors.forename: Dimitrios T
authors.initials: DT
authors.lastname: Boumpas
authors.forename: George N
authors.initials: GN
authors.lastname: Goulielmos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016001:Confidence Intervals; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006115:Greece / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D020080:Tandem Repeat Sequences
chemical_list: C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III