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The association between glutathione S-transferase T1 and M1 gene polymorphisms and microalbuminuria and incipient nephropathy in children with type 1 diabetes mellitus


Authors: J. Vojtková;  M. Čiljaková;  P. Ďurdík;  Z. Michnová;  T. Turčan
Authors‘ workplace: Klinika detí a dorastu, Univerzita Komenského v Bratislave, Jesseniova lekárska fakulta a Univerzitná nemocnica Martin prednosta prof. MUDr. P. Bánovčin, CSc.
Published in: Čes-slov Pediat 2013; 68 (2): 92-100.
Category: Original Papers

Overview

Oxidative stress is discussed factor in the etiopathogenesis of diabetic nephropathy (DN). Glutathione S-transferase (GST) represents the family of multifunctional isoenzymes with antioxidant function. The most researched isoenzymes are glutathione S-transferase theta 1 (GST T1) and mu 1 (GST M1) while null polymorphisms are associated with lower activity of these enzymes. The aim of this work was to establish, whether GST T1 and M1 gene polymorphisms were linked to presence of microalbuminuria and diabetic nephropathy in children with type 1 diabetes.

In 116 patients with type 1 diabetes at the age 6–19 years, basic anthropometric parameters were noticed, glycosylated hemoglobin was examined by standard biochemical methods and microalbuminuria was examined from 12-hour night urine sample. Incipient nephropathy was diagnosed as repeated finding of microalbuminuria of 20–200 μg/min. GST T1 and M1 gene polymorphisms were established by polymerase chain reaction.

Children with GST T1 null genotype (n=42) had significantly higher microalbuminuria compared to the subjects with GST T1 wild genotype (n=74) (p<0.05). No significant difference was found in other measured parameters. Similarly, no significant difference was estimated in measured parameters between subjects regarding GST M1 genotype. Incipient nephropathy was diagnosed in 26 children (22.41%). Patients with diabetic nephropathy (DN+) had significantly higher age (p<0.01), longer diabetes duration (p<0.01), higher body mass index (p<0.01) and higher microalbuminuria (p<0.01) compared to patients without nephropathy (DN-). These parameters were confirmed as risk factors for DN origin by multivariate logistic regression. Differences in gene polymorphisms between DN+ and DN- subgroups were not significant.

GST T1 null genotype may be associated with higher microalbuminuria, however further studies are necessary to confirm this indication.

Key words:
diabetic nephropathy, gene polymorphisms, glutathione S-transferase T1 and M1


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