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

Autor: Rehořová J, Jan Svojanovský, Jindřich Olšovský, Katarína Kuricová, Tanhäuserová, Lukáš Pácal, Kateřina Kaňková, Martin Klepárník, Soňa Štěpánková, Jan Mužík, Tomáš Pavlík, Denisa Malúšková, Jana Bělobrádková, Bartáková, Darja Krusová, Michal Jurajda, Josef Tomandl
Rok vydání: 2012
Předmět:
Adult
Male
medicine.medical_specialty
Population
Single-nucleotide polymorphism
Type 2 diabetes
030204 cardiovascular system & hematology
Arginine
Methylation
Polymorphism
Single Nucleotide
Amidohydrolases
Diabetic nephropathy
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Predictive Value of Tests
Risk Factors
Internal medicine
medicine
SNP
Humans
Diabetic Nephropathies
education
030304 developmental biology
Aged
Czech Republic
0303 health sciences
education.field_of_study
Reproducibility of Results
General Medicine
Middle Aged
medicine.disease
Prognosis
3. Good health
Endocrinology
Cross-Sectional Studies
Diabetes Mellitus
Type 1
chemistry
Diabetes Mellitus
Type 2
Nephrology
Multivariate Analysis
Albuminuria
Disease Progression
Female
medicine.symptom
Cardiology and Cardiovascular Medicine
Asymmetric dimethylarginine
Kidney disease
Follow-Up Studies
Zdroj: Kidneyblood pressure research. 36(1)
ISSN: 1423-0143
Popis: 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.
Databáze: OpenAIRE
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