Relationship between DDAH gene variants and serum ADMA level in individuals with type 1 diabetes.

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).

Sequence variation in DDAH1 and DDAH2 genes is strongly and additively associated with serum ADMA concentrations in individuals with type 2 diabetes.

Background: 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.

Diabetic retinopathy is associated with elevated serum asymmetric and symmetric dimethylarginines.

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.