Javadiyan, S and Burdon, KP and Whiting, MJ and Abhary, S and Straga, T and Hewitt, AW and Mills, RA and Craig, JE, Elevation of serum asymmetrical and symmetrical dimethylarginine in patients with advanced glaucoma, Investigative Ophthalmology & Visual Science, 53, (4) pp. 1923-1927. ISSN 1552-5783 (2012) [Refereed Article]
Copyright 2012 The Association for Research in Vision and Ophthalmology Inc.
Purpose: 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.
|Item Type:||Refereed Article|
|Research Division:||Medical and Health Sciences|
|Research Group:||Ophthalmology and Optometry|
|Objective Group:||Clinical Health (Organs, Diseases and Abnormal Conditions)|
|Objective Field:||Hearing, Vision, Speech and Their Disorders|
|Author:||Burdon, KP (Associate Professor Kathryn Burdon)|
|Author:||Hewitt, AW (Professor Alex Hewitt)|
|Web of Science® Times Cited:||15|
|Deposited By:||Menzies Institute for Medical Research|
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