title: Relationship between DDAH gene variants and serum ADMA level in individuals with type 1 diabetes.
abstract: 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.
authors.affiliation: Department of Ophthalmology, Flinders Medical Centre and Flinders University, South Australia, Australia.
authors.forename: Rhys D
authors.initials: RD
authors.lastname: Fogarty
authors.forename: Sotoodeh
authors.initials: S
authors.lastname: Abhary
authors.forename: Shahrbanou
authors.initials: S
authors.lastname: Javadiyan
authors.forename: Nicholas
authors.initials: N
authors.lastname: Kasmeridis
authors.forename: Nikolai
authors.initials: N
authors.lastname: Petrovsky
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Whiting
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Craig
authors.forename: Kathryn P
authors.initials: KP
authors.lastname: Burdon
mesh_terms: D000328:Adult; D000368:Aged; D000581:Amidohydrolases / Q000235:genetics*; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015331:Cohort Studies; D048909:Diabetes Complications / Q000097:blood / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000502:physiology
chemical_list: C018524:N,N-dimethylarginine; D001120:Arginine; D000581:Amidohydrolases; C059999:dimethylargininase