title: NOS3 894G>T polymorphism is associated with progression of kidney disease and cardiovascular morbidity in type 2 diabetic patients: NOS3 as a modifier gene for diabetic nephropathy?
abstract: OBJECTIVE
  We have previously associated SNP 894G>T in the NOS3 gene with diabetic nephropathy (DN) using multi-locus analysis. Variant 894G>T has been widely studied as a DN susceptibility factor with contradictory results. In the present study we genotyped 894G>T in the cohort of prospectively followed type 2 diabetics with the aim to investigate its possible role in the progression of DN and development of morbidity and mortality associated with diabetes.
  
  
  METHODS
  311 subjects with defined stage of DN were enrolled in the study and followed up for a median of 38 months. We considered three end-points: progression of DN, major cardiovascular event and all-cause mortality.
  
  
  RESULTS
  Considering baseline GFR, age at enrolment and diabetes duration as confounders, Cox regression analysis identified 894GT genotype as a risk factor for DN progression (HR = 1.843 [95% CI 1.088 - 3.119], P = 0.023) and 894TT genotype as a risk factor for major cardiovascular event (HR = 2.515 [95% CI 1.060 - 5.965], P = 0.036).
  
  
  CONCLUSIONS
  We ascertained the significant effect of the NOS3 894G>T variant on DN progression and occurrence of major cardiovascular event in T2DM subjects. Based on these results NOS3 can be considered a modifier gene for DN.
authors.affiliation: Department of Pathophysiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Katarína
authors.initials: K
authors.lastname: Kuricová
authors.forename: Veronika
authors.initials: V
authors.lastname: Tanhäuserová
authors.forename: Lukáš
authors.initials: L
authors.lastname: Pácal
authors.forename: Vendula
authors.initials: V
authors.lastname: Bartáková
authors.forename: Lucie
authors.initials: L
authors.lastname: Brožová
authors.forename: Jiří
authors.initials: J
authors.lastname: Jarkovský
authors.forename: Kateřina
authors.initials: K
authors.lastname: Kaňková
mesh_terms: D000368:Aged; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology* / Q000235:genetics*; D058065:Diabetic Cardiomyopathies / Q000201:enzymology / Q000453:epidemiology* / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D011446:Prospective Studies
chemical_list: C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III