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Asymmetric dimethylarginine (ADMA) levels are elevated in diabetes and likely contribute to diabetic complications such as retinopathy and nephropathy. The DDAH enzymes are primarily responsible for ADMA metabolism. Polymorphisms in the dimethylarginine dimethylaminohydrolase (DDAH) 1 and 2 genes have been previously associated with serum ADMA levels in type 2 diabetes (T2DM). We sought to determine whether they are also associated with ADMA levels in individuals with type 1 diabetes (T1DM). Serum ADMA concentrations were measured in 196 individuals with T1DM. Twenty-six tag SNPs in the DDAH1 gene and 10 in the DDAH2 gene were genotyped. One SNP in the DDAH1 gene (rs3738111) and one in the DDAH2 gene (rs805293) showed a correlation with serum ADMA levels; however, neither survived correction for multiple testing. We found limited evidence that genetic polymorphisms in DDAH genes influence serum ADMA levels in individuals with T1DM. This differs to findings in T2DM and may be due to underlying differences in the cohorts or to fundamental differences in the pathogenesis of the two types of diabetes.

Copyright: © 2010 Abhary et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited., Asymmetric dimethylarginine (ADMA), present in human serum, is an endogenous inhibitor of nitric oxide synthase and contributes to vascular disease. Dimethylarginine dimethylaminohydrolase (DDAH) is an ADMA degrading enzyme that has two isoforms: DDAHI and DDAHII. We sought to determine whether serum ADMA levels in type 2 diabetes are influenced by common polymorphisms in the DDAH1 and DDAH2 genes.

OBJECTIVE Asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and l-arginine directly influence nitric oxide production. Our objective was to test whether serum ADMA, SDMA, or l-arginine levels correlate with diabetic retinopathy subtype or severity. RESEARCH DESIGN AND METHODS A total of 162 subjects with type 1 diabetes and 343 with type 2 diabetes, of whom 329 subjects had no diabetic retinopathy, 27 had nonproliferative diabetic retinopathy (NPDR), 101 had proliferative diabetic retinopathy (PDR), and 107 had clinically significant macular edema (CSME), were recruited. Blinding diabetic retinopathy was defined as severe NPDR, PDR, or CSME. Serum ADMA, SDMA, and l-arginine concentrations were determined by mass spectroscopy. RESULTS In multivariate analysis, blinding diabetic retinopathy, PDR, and nephropathy were associated with significantly increased serum levels of ADMA (P < 0.001), SDMA (P < 0.001), and l-arginine (P = 0.001). Elevated ADMA (P < 0.001) and SDMA (P < 0.001) were also significantly associated with CSME. CONCLUSIONS Severe forms of diabetic retinopathy are associated with elevated serum ADMA, SDMA, and l-arginine. Further investigation is required to determine whether these findings are of clinical relevance.