Academic journal article Central European Journal of Public Health

The Association between Gene Polymorphisms of Glutathione S-Transferase T1/m1 and Type 1 Diabetes in Slovak Children and Adolescents

Academic journal article Central European Journal of Public Health

The Association between Gene Polymorphisms of Glutathione S-Transferase T1/m1 and Type 1 Diabetes in Slovak Children and Adolescents

Article excerpt

SUMMARY

Background: Considering a dramatic increase in the incidence of type 1 diabetes (T1D) worldwide, current research focuses on complex etiology of T1D where immune system, environmental and genetic factors play a significant role. Glutathione S-transferase family of enzymes protects tissue from oxidative damage which is discussed in the context of T1D. The aim of the study was to investigate an association of glutathione S-transferase mu 1 (GST M1) and glutathione S-transferase theta 1 (GST T1) polymorphisms with type 1 diabetes.

Methods: 163 children, 116 with type 1 diabetes and 47 healthy controls, at the age 6-19 years were enrolled to the study. Basic anthropometric, biochemical parameters and GST T1 diabetes and M1 polymorphisms were established in each subject.

Results: Subjects with T1D had significantly lower concentration of uric acid compared to the healthy subjects (212.85±57.10 μmοl/l vs. 269.57±72.53; p<0.001). GST T1 null genotype was more frequent in patients with diabetes compared to the healthy controls (36.2% vs. 21.3%) and represented 2.1-fold increased risk of T1D of borderline statistical significance (OR=2.1; 95% CI=0.949-4.648; p=0.06). GSTT1 null/M1 wild genotype combination was more frequent in patients with diabetes (25.9% vs. 10.6%) and represented 2.9-fold increased risk for T1D development (OR=2.93; 95% Cl=1.061-8.095; p=0.032).

Conclusion: The study indicates that GST T1 null genotype and GST T1 null/M1 wild combination could be considered a risk factor for type 1 diabetes development in Slovak children and adolescents.

Key words: type 1 diabetes, glutathione S-transferase T1 and M1, gene polymorphisms

INTRODUCTION

Epidemiological studies indicate that the incidence and prevalence of type 1 diabetes mellitus (T1D) is rising worldwide. The incidence rate of childhood T1D across Europe rises nonuniformly every year by an average of 3-4% (1). In Slovakia, a 2.57-fold increase in the incidence of T1D from 1986 to 1998 was the highest among children 10-14 years of age and increased dramatically especially in children CM- years old (2). Although significant effort has been made to improve the quality of life and clinical outcomes in patients with Τ ID, much more needs to be done to find the prevention and cure of T1D. Therefore, research of risk factors of T1D is necessary to identify triggers that could potentially be targeted for intervention. Current studies focus on predisposing factors in complex etiology of T1D, where immune system, environmental triggers and genetic susceptibility play a significant role. One of the pathways discussed in the etiopathogenesis of T1D is oxidative stress (3) characterized as an imbalance between reactive oxygen species (ROS) production and antioxidant mechanisms. ROS are liberated by activated macrophages and Τ lymphocytes and are induced by proinflammatory cytokines involved in autoimmune process of pancreatic beta cells. An increased level of ROS causes oxidative modification of proteins and nucleic acids and lipid peroxidation. These changes may result in alteration in biological functions of all biomolecules, in metabolism of all tissues and cell damage including beta cells.

Glutathione S-transferase (GST) represents a family of enzymes catalyzing the conjugation of glutathione with various electrophilic compounds to facilitate their excretion (4). The broad substrate specificity of GSTs allows them to protect cells against a range of toxic chemicals, however, this GST activity can be deleterious in certain cases, as it can cause chemotherapy resistance or the arisen metabolite can be more toxic than the primary molecule (5). GST enzymes are involved in the synthesis of inflammatory mediators, leukotrienes and prostaglandins and act also in cell signaling pathway as potential regulators of apoptosis. Regarding their function within oxidative stress, GSTs detoxify some of the secondary ROS generated during oxidation of membranes or other cellular constituents. …

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