title: A functional variant of the dimethylarginine dimethylaminohydrolase-2 gene is associated with chronic kidney disease.
abstract: OBJECTIVE
  Studies reported a relationship between elevated asymmetric dimethylarginine (ADMA) concentrations and adverse renal outcomes. There is evidence that the rs9267551 variant in the DDAH2 gene has a functional impact with the C allele having a higher transcriptional activity resulting in increased expression of DDAH2 in endothelial cells and lower plasma ADMA levels in C allele carriers.
  
  
  METHODS
  To address whether this variant is associated with chronic kidney disease (CDK), 2852 White European were studied. CKD was defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2).
  
  
  RESULTS
  The proportion of subjects with CKD was significantly lower in C allele carriers than in GG genotype carriers (OR 0.49, 95%CI 0.25-0.97; P = 0.03). In a logistic regression model adjusted for age, gender, BMI, blood pressure, total and HDL cholesterol, triglyceride, and fasting plasma glucose, C allele carriers have a lower risk of CKD compared with GG genotype carriers (OR 0.38, 95%CI 0.18-0.78; P = 0.008). This association was maintained after addition to the logistic regression model of other confounders including glucose tolerance status, presence of dyslipidemia, anti-hypertensive and antidiabetic drugs (OR 0.35, 95%CI 0.15-0.80; P = 0.01).
  
  
  CONCLUSIONS
  The rs9267551 functional variant of the DDAH2 gene is associated with CKD with carriers of the C allele having a lower risk of renal dysfunction independently from several confounders. Because ADMA predicted progression of renal disease, it is possible that, in GG carriers, ADMA may accumulate at the renal level causing endothelial dysfunction as a consequence of reduced nitric oxide availability and potentiating micro-vascular damage.
authors.affiliation: Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Via Europa-Località Germaneto, Catanzaro 88100, Italy. Electronic address: sesti@unicz.it.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Sesti
authors.forename: Gaia Chiara
authors.initials: GC
authors.lastname: Mannino
authors.forename: Carlo
authors.initials: C
authors.lastname: De Lorenzo
authors.forename: Annalisa
authors.initials: A
authors.lastname: Greco
authors.forename: Angela
authors.initials: A
authors.lastname: Sciacqua
authors.forename: Maria A
authors.initials: MA
authors.lastname: Marini
authors.forename: Francesco
authors.initials: F
authors.lastname: Andreozzi
authors.forename: Francesco
authors.initials: F
authors.lastname: Perticone
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000581:Amidohydrolases / Q000235:genetics*; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000201:enzymology / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: C018524:N,N-dimethylarginine; D001120:Arginine; D000581:Amidohydrolases; C059999:dimethylargininase
keywords: Asymmetric dimethylarginine; Chronic kidney disease; Dimethylarginine dimethylaminohydrolase