ADMA, SDMA and L-arginine/ADMA ratio but not DDAH genetic polymorphisms are reliable predictors of diabetic nephropathy progression as identified by competing risk analysis

• Authors: TANHÄUSEROVÁ Veronika; TOMANDL Josef; PÁCAL Lukáš; KLEPÁRNÍK Martin; MALÚŠKOVÁ Denisa; BARTÁKOVÁ Vendula; KURICOVÁ Katarína; ŘEHOŘOVÁ Jitka; ŠTĚPÁNKOVÁ Soňa; SVOJANOVSKÝ Jan; OLŠOVSKÝ Jindřich; BĚLOBRÁDKOVÁ Jana; KRUSOVÁ Darja; JURAJDA Michal; MUŽÍK Jan; PAVLÍK Tomáš; KAŇKOVÁ Kateřina
• Year of publication: 2012
• Type: Article in Periodical
• Magazine / Source: KIDNEY & BLOOD PRESSURE RESEARCH
• MU Faculty or unit: Faculty of Medicine
• Web: http://www.karger.com/Article/Pdf/343409
• Doi: http://dx.doi.org/10.1159/000343409
• Field: Endocrinology, diabetology, metabolism, nutrition
• Keywords: asymmetric dimethylarginine; competing risk analysis; diabetic nephropathy; dimethylarginine dimethylaminohydrolase; polymorphism; symmetric dimethylarginine
• Description: Background/Aims: Complex interplay of genetic and (patho)physiological factors influence availability of nitric oxide during the development and progression of diabetic complications. We assessed predictive value of commonly studied methylated asymmetric and symmetric dimethylarginines (ADMA and SDMA) and selected single nucleotide polymorphisms (SNPs) in dimethylarginine dimethylaminohydrolase (DDAH) 1 and 2 genes for the progression of diabetic nephropathy (DN). Methods: A total of 341 type 1 and type 2 diabetes patients with variable degree of kidney disease were included at baseline. Plasma levels of ADMA, SDMA and L-arginine were measured and six tagging SNPs in DDAH1 and 2 were determined. Progression of DN was defined as a transition from any given stage to a more advanced stage of albuminuria. Competing risk analysis was applied. Results: Plasma levels of ADMA and SDMA significantly correlated with GFR. No significant genotype-phenotype relationship was ascertained for ADMA and DDAH variants, but SNP rs805304 exhibited marginally significant association with DN. ADMA, SDMA and L-arginine/ADMA ratio standardised to GFR were identified as significant predictors of DN progression but not GFR decline using multivariate competing risk analysis. Conclusions: In our study we confirmed potentially significant role of ADMA and SDMA for the assessment of risk of DN progression in European diabetic population.

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