title: DDAH gene and cardiovascular risk.
abstract: The crucial role of nitric oxide (NO) for normal endothelial function is well known. In many conditions associated with increased risk of cardiovascular diseases such as hypercholesterolemia, hypertension, abdominal obesity, diabetes and smoking, NO biosynthesis is dysregulated, leading to endothelial dysfunction. The growing evidence from animal and human studies indicates that endogenous inhibitors of endothelial NO synthase such as asymmetric dimethylarginine (ADMA) and NG-monomethyl-L-arginine (L-NMMA) are associated with the endothelial dysfunction and potentially regulate NO synthase. The major route of elimination of ADMA is metabolism by the enzymes dimethylarginine dimethylaminohydrolase-1 and -2 (DDAH). In our recent study 16 men with either low or high plasma ADMA concentrations were screened to identify DDAH polymorphisms that could potentially be associated with increased susceptibility to cardiovascular diseases. In that study a novel functional mutation of DDAH-1 was identified; the mutation carriers had a significantly elevated risk for cardiovascular disease and a tendency to develop hypertension. These results confirmed the clinical role of DDAH enzymes in ADMA metabolism. Furthermore, it is possible that more common variants of DDAH genes contribute more widely to increased cardiovascular risk.
authors.affiliation: The Research Institute of Public Health, University of Kuopio, Finland. Velipekka.Valkonen@uku.fi
authors.forename: Veli-Pekka
authors.initials: VP
authors.lastname: Valkonen
authors.forename: Tomi-Pekka
authors.initials: TP
authors.lastname: Tuomainen
authors.forename: Reijo
authors.initials: R
authors.lastname: Laaksonen
mesh_terms: D000581:Amidohydrolases / Q000235:genetics* / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000201:enzymology / Q000235:genetics; D008297:Male; D009154:Mutation; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: C018524:N,N-dimethylarginine; D001120:Arginine; D000581:Amidohydrolases; C059999:dimethylargininase