To investigate determinants of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), including single nucleotide polymorphisms (SNPs), in the DDAH1, DDAH2, and AGXT2 genes and their associations with prevalent and incident cardiovascular disease (CVD) in older adults with type 2 diabetes mellitus.
These results indicate that suppression of DDAH2 expression is a culprit for homocysteine-induced impairments of DDAH/ADMA/NOS/NO pathway in endothelial cells, and therapeutic manipulation of DDAH2 expression may be a promising strategy for preventing endothelial dysfunction and cardiovascular diseases associated with hyperhomocysteinemia.
The discovery of a functional polymorphism within the DDAH2 promoter suggests that there may be common, individual differences in the ability to metabolise ADMA in vivo, that in turn, might underlie susceptibility to cardiovascular disease.