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

Vesna Ilić; Miroljub Ilić; Ivan Soldatović; Srdjan Popović; Zvonko Magić

doi:10.2298/2743

Vesna Ilić Institute for Medical Research, Military Medical Academy, Belgrade, Serbia
Miroljub Ilić Institute for Endocrinology, Diabetes and Medical Research, Clinical Center of Serbia, Belgrade, Serbia
Ivan Soldatović Institute for Medical Statistics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
Srdjan Popović Institute for Endocrinology, Diabetes and Medical Research, Clinical Center of Serbia, Belgrade, Serbia
Zvonko Magić Institute for Medical Research, Military Medical Academy, Belgrade, Serbia; Faculty of Medicine of the Military Medical Academy, University of Defence, Belgrade, Serbia

DOI: https://doi.org/10.2298/2743

Keywords: diabetic nephropathies, renin-angiotensin system, diabetes mellitus, type 1, polymorphism, genetic,

Abstract

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 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.

Author Biography

Vesna Ilić, Institute for Medical Research, Military Medical Academy, Belgrade, Serbia

Odsek za molekulsku medicinu

Biolog

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