Diabetic nephropathy - Pharmacogenomics and variability in genes of renin-angiotensin-aledosterone system

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Authors

BARTÁKOVÁ Vendula TANHÄUSEROVÁ Veronika PÁCAL Lukáš KURICOVÁ Katarína LINHARTOVÁ Petra KAŇKOVÁ Kateřina

Year of publication 2011
Type Conference abstract
MU Faculty or unit

Faculty of Medicine

Citation
Description Diabetic nephropathy (DN) is one of the most common and serious complications of diabetes mellitus with pathological activation of renin-angiotensin-aldosterone system (RAAS) as the key pathogenetic mechanism. Pharmacological blockade of RAAS represents the main renoprotective treatment of DN. Several single nucleotide polymorphisms (SNPs) were shown to influence interindividual variability of RAAS (e.g circulating levels of RAAS compounds and enzyme activities). These functional genetic variants are supposed to modify therapeutic effect of RAAS blockers. Genetic variability together with other factors, which are objects of therapeutical compensation (e.g. glycaemia, blood pressure, proteinuria, lipidaemia and body weight) can affect progression of kidney damage in diabetics. The aim of this project is to study the effect of genetic variability in the selected components of RAAS in the progression of kidney disease by diabetic patients. Three SNPs in angiotensin converting enzyme (ACE - rs4343), angiotensinogen (ATG M235T - rs699) and angiotensin II type I receptor gene (ATR1 A1166C - rs5186) were genotyped using restriction fragment length polymorphism PCR. This case – case study involved 433 patients with a different degree of DN. Results of the haplotype analysis will be compared with a pharmacological treatment - especially RAAS blockers. We expect a variability of haplotypes in RAAS genes among patients with different degree of DN and a possibility of an implementation of phamacogenomic approach to the treatment of DN.
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