title: ADMA, SDMA and L-arginine/ADMA ratio but not DDAH genetic polymorphisms are reliable predictors of diabetic nephropathy progression as identified by competing risk analysis.
abstract: OBJECTIVE
  Complex interplay of genetic and (patho)physiological factors influence availability of nitric oxide during the development and progression of diabetic complications. We assessed predictive value of commonly studied methylated asymmetric and symmetric dimethylarginines (ADMA and SDMA) and selected single nucleotide polymorphisms (SNPs) in dimethylarginine dimethylaminohydrolase (DDAH) 1 and 2 genes for the progression of diabetic nephropathy (DN).
  
  
  METHODS
  A total of 341 type 1 and type 2 diabetes patients with variable degree of kidney disease were included at baseline. Plasma levels of ADMA, SDMA and L-arginine were measured and six tagging SNPs in DDAH1 and 2 were determined. Progression of DN was defined as a transition from any given stage to a more advanced stage of albuminuria. Competing risk analysis was applied.
  
  
  RESULTS
  Plasma levels of ADMA and SDMA significantly correlated with GFR. No significant genotype-phenotype relationship was ascertained for ADMA and DDAH variants, but SNP rs805304 exhibited marginally significant association with DN. ADMA, SDMA and L-arginine/ADMA ratio standardised to GFR were identified as significant predictors of DN progression but not GFR decline using multivariate competing risk analysis.
  
  
  CONCLUSIONS
  In our study we confirmed potentially significant role of ADMA and SDMA for the assessment of risk of DN progression in European diabetic population.
authors.affiliation: Dept. of Pathophysiology, Masaryk University Brno, Czech Republic. veronika.tan@mail.muni.cz
authors.forename: Veronika
authors.initials: V
authors.lastname: Tanhäuserová
authors.forename: Josef
authors.initials: J
authors.lastname: Tomandl
authors.forename: Lukáš
authors.initials: L
authors.lastname: Pácal
authors.forename: Martin
authors.initials: M
authors.lastname: Klepárník
authors.forename: Denisa
authors.initials: D
authors.lastname: Malúšková
authors.forename: Vendula
authors.initials: V
authors.lastname: Bartáková
authors.forename: Katarína
authors.initials: K
authors.lastname: Kuricová
authors.forename: Jitka
authors.initials: J
authors.lastname: Rehořová
authors.forename: Soňa
authors.initials: S
authors.lastname: Stěpánková
authors.forename: Jan
authors.initials: J
authors.lastname: Svojanovský
authors.forename: Jindřich
authors.initials: J
authors.lastname: Olšovský
authors.forename: Jana
authors.initials: J
authors.lastname: Bělobrádková
authors.forename: Darja
authors.initials: D
authors.lastname: Krusová
authors.forename: Michal
authors.initials: M
authors.lastname: Jurajda
authors.forename: Jan
authors.initials: J
authors.lastname: Mužík
authors.forename: Tomáš
authors.initials: T
authors.lastname: Pavlík
authors.forename: Kateřina
authors.initials: K
authors.lastname: Kaňková
mesh_terms: D000328:Adult; D000368:Aged; D000581:Amidohydrolases / Q000235:genetics*; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood* / Q000235:genetics; D003430:Cross-Sectional Studies; D018153:Czech Republic; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D003928:Diabetic Nephropathies / Q000097:blood / Q000209:etiology / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008745:Methylation; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011237:Predictive Value of Tests; D011379:Prognosis; D015203:Reproducibility of Results; D012307:Risk Factors
chemical_list: C024917:symmetric dimethylarginine; C018524:N,N-dimethylarginine; D001120:Arginine; D000581:Amidohydrolases; C059999:dimethylargininase