Association of renin-angiotensin system genes polymorphism with progression of diabetic nephropathy in patients with type 1 diabetes mellitus

Vesna Ilic, Miroljub Ilic, Ivan Soldatovic, Srdjan Popovic, Zvonko Magic
2014 Vojnosanitetski Pregled  
Background/Aim. Diabetic nephropathy (DN) as a major microvascular complication of diabetes mellitus (DM) include a progressive increase in urinary albumin excretion in association with an increase in blood pressure and to end stage renal failure. Hypertension connected with renin-angiotensin system (RAS) hyperactivity and corresponding genotypes, angiotensinogen (AGT), angiotensine-converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R), predispose the increasing risk of DN. The aim
more » ... isk of DN. The aim of this study was to assess the distribution of AGT, ACE and AT1R gene polymorphisms in patients with type 1 DM according to the level of DN and patients clinical characteristics. Methods. The study included 79 type 1 diabetic patients. Inclusion criteria were: age between 20-40, duration of diabetes > 5 years, and no other severe diseases. Clinical characteristics were gained from interviewing the patients. Polymorphism was detected by polymerase chain reaction (PCR) and restriction fragment length polymorphism using restriction enzymes Psy I (Tth 111 I) and Hae III. Results. The patients with proteinuria compared with normo-and microalbuminuric patients, highly differed in age, diabetes duration, blood pressure level, hypertension, rethynopathy and urinary albumin excretion values (p < 0.001). No statistically significant difference between the groups was found for the ACE and AT1R gene polymorphisms distribution. The presence of TT genotype of the M235T polymorphism was significantly higher in the group with proteinuria (p < 0.05). The patients with hypertension raised nephropathy 5.2 times higher (OR = 5.20, p < 0.05) while carriers of TT allel developed nephropathy 28.38 times higher (OR = 28.389, p < 0.01) than those with MM genotype. Conclusion. Increased association of hypertension and TT angiotensinogen gene polymorphism in patients with diabetes mellitus with proteinuria could be a significant marker of diabetic nephropathy. Apstrakt Strana 628 VOJNOSANITETSKI PREGLED Volumen 71, Broj 7 Ili V, et al. Vojnosanit Pregl 2014; 71(7): 627-633. zna ajne. Prisustvo TT genotipa u M235T polimorfizmu gena za AGT bio je zna ajno viši u grupi bolesnika sa proteinurijom (p < 0,05). U estalost nefropatije bila je 5,2 puta ve a (OR = 5,20, p < 0,05) kod dijabeti ara sa hipertenzijom, dok je TT genotip ukazivao na 28.38 puta ve u sklonost (OR = 28,389, p < 0,01) ka razvoju nefropatije u odnosu na MM genotip. Zaklju ak. Pove anje u estalosti hipertenzije i TT alelske forme u angiotenzinogen gen-skom polimorfizmu kod bolesnika u terminalnom stadijumu nefropatije mogu imati zna aj za odre ivanje markera procene rizika od nastanka komplikacija u dijabetesu melitusu tipa 1. Klju ne re i: dijabeti ke nefropatije; renin-angiotenzin sistem; dijabetes melitus, tip 1; polimorfizam, geneti ki.
doi:10.2298/vsp1407627i pmid:25109108 fatcat:al6b7wntozemhhmu2eabfd7ypq