sequence variation in ddah1 and ddah2 genes is strongly and additively associated with serum adma concentrations in individuals with type 2 diabetes序列变化ddah1基因ddah2强烈和加法与血清adma浓度在2型糖尿病患者.pdfVIP

Sequence Variation in DDAH1 and DDAH2 Genes Is Strongly and Additively Associated with Serum ADMA Concentrations in Individuals with Type 2 Diabetes 1 1 1 1 3 Sotoodeh Abhary *, Kathryn P. Burdon , Abraham Kuot , Shahrbanou Javadiyan , Malcolm J. Whiting , 2 2 1 Nicholas Kasmeridis , Nikolai Petrovsky , Jamie E. Craig 1 Department of Ophthalmology, Flinders Medical Centre and Flinders University, Adelaide, South Australia, Australia, 2 Department of Endocrinology, Flinders Medical Centre and Flinders University, Adelaide, South Australia, Australia, 3 Chemical Pathology Laboratory, SA Pathology, Adelaide, South Australia, Australia Abstract 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. Methodology/Principal Findings: Relevant clinical parameters were measured and peripheral whole blood obtained for serum and genetic analysis on 343 participants with type 2 diabetes. Serum ADMA concentrations were determined by mass spectroscopy. Twenty six tag SNPs in the DDAH1 and 10 in the DDAH2 gene were genotyped in all subjects and tested for association with serum ADMA levels. Several SNPs and haplotypes in the DDAH genes were strongly associated with ADMA levels. Most significantly in the DDAH1 gene, rs669173 (p = 2.96 61027), rs7521189 (p =