title: Elevation of serum asymmetrical and symmetrical dimethylarginine in patients with advanced glaucoma.
abstract: OBJECTIVE
  Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) are the dimethylated isomeric derivatives of the amino acid L-arginine. ADMA is an endogenous inhibitor of nitric oxide synthase (NOS), while SDMA is a competitive inhibitor of cellular uptake of L-arginine, the substrate for NOS. As such, these metabolites are associated with endothelial dysfunction. As the nitric oxide pathway and endothelial dysfunction have been implicated in glaucoma, the aim of this study was to investigate serum ADMA, SDMA, and L-arginine levels in individuals with advanced glaucoma compared with normal controls. In addition, we have investigated genetic variation in the DDAH1 and DDAH2 genes, encoding the enzymes responsible for degradation of ADMA, for association with ADMA level in glaucoma patients and controls.
  
  
  METHODS
  Two hundred eleven patients with advanced glaucoma and 295 normal controls were recruited. Liquid chromatography-tandem mass spectrometry was used to measure the serum ADMA, SDMA, and L-arginine levels of participants. Single nucleotide polymorphisms in the DDAH1 and DDAH2 genes reportedly associated with ADMA level were genotyped in all individuals.
  
  
  RESULTS
  A significant increase in both serum ADMA and SDMA concentration was detected in advanced glaucoma cases compared with controls (P ≤ 0.0001). No significant change was detected in serum L-arginine concentration. No association of polymorphisms in DDAH1 and DDAH2 with either ADMA level or glaucoma was detected.
  
  
  CONCLUSIONS
  The serum levels of two dimethylarginines, ADMA and SDMA, are associated with advanced glaucoma. These data further implicate the nitric-oxide pathway in glaucoma pathogenesis.
authors.affiliation: Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, Australia.
authors.forename: Shahrbanou
authors.initials: S
authors.lastname: Javadiyan
authors.forename: Kathryn P
authors.initials: KP
authors.lastname: Burdon
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Whiting
authors.forename: Sotoodeh
authors.initials: S
authors.lastname: Abhary
authors.forename: Tania
authors.initials: T
authors.lastname: Straga
authors.forename: Alex W
authors.initials: AW
authors.lastname: Hewitt
authors.forename: Richard A
authors.initials: RA
authors.lastname: Mills
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Craig
mesh_terms: D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D005901:Glaucoma / Q000097:blood* / Q000503:physiopathology; D006801:Humans; D007429:Intraocular Pressure; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D012189:Retrospective Studies; D012720:Severity of Illness Index; D053719:Tandem Mass Spectrometry
chemical_list: D015415:Biomarkers; C024917:symmetric dimethylarginine; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase