Study of the association between glutathione S-transferase (GSTM1, GSTT1, GSTP1) polymorphisms with type II diabetes mellitus in southern of Iran

Abstract

Diabetes Mellitus is characterized by chronic hyperglycemia and associated with an increased production of reactive oxygen species (ROS). Oxidative stress is the result of accumulation of free radicals in tissues which specially affects beta cells in pancreas. Glutathione S-transferases (GSTs) are a family of antioxidant enzymes that include several classes of GSTs. These enzymes have important roles in decreasing of ROS species and act as a kind of antioxidant defense. To investigate the association between GSTs polymorphism with type 2 diabetes mellitus (T2DM), we investigated the frequency of GSTM1, T1 and P1 genotypes in patients with T2DM and controls. The genotypes of GSTT1, M1 and P1 were determined in 171 clinically documented T2DM patients and 169 normal cases (as controls) by multiplex polymerase chain reaction and PCR-RFLP. In diabetic patients, the frequency of GSTM1-null genotype was significantly (OR = 1.74; 95 % CI = 1.13-2.69, P = 0.016) higher than that in control. However, the frequency of GSTT1 (OR = 1.29; 95 % CI = 0.07-2.14, P = 0.367) and GSTP1 (OR = 0.83; 95 % CI = 0.53-1.30, P = 0.389) genotypes were not significantly different comparing both groups. Also, the frequency of both GSTT1-null and GSTM1-null genotypes in patients (19.88 %) was significantly higher compared to controls with the same genotypes (11.83 %, P = 0.022). Our results indicated that GSTM1 and GSTT1 genotypes might be involved in the pathogenesis of T2DM in south Iranian population.

Activities of Three Erythrocyte Enzymes of Hyperglycemic Rats (Rattus norvegicus) Treated with Allium sativa Extract.

“…[60] In a related perspective, the use of GT activity as a reliable biomarker in depicting the etiology of diabetes mellitus has been described. [2] It was posited that two isoforms of GST (GSTM1 and GSTT1) might be involved in the pathogenesis of Type 2 diabetes mellitus in a South Iranian population. In addition, investigations have shown that the GSTM1 gene may play a significant role in the aetiopathogeneses of diabetes mellitus and could serve as a useful biomarker in the prediction of diabetes mellitus susceptibility of the Turkish population.…”

“…Primarily, overall physiologic distortions prompted by poor control of metabolism in the absence or insufficiency of insulin engender hyperglycemia and associated metabolic disorders. [1,2] Striking consequential effects of prolonged hyperglycemia include changes in the structure and function of macromolecules, [3,4] auto-oxidation of glycated proteins, increased production of reactive oxygen species (ROS), decreased antioxidant defense, increased lipid peroxidation, and associated apoptosis or necrosis occasioned by membrane degeneration. [4,5] Notably, alterations/adjustments in most glycolytic and tricarboxylic acid cycle (TCA) enzyme activities are associated with diabetic states.…”

“…These enzymes by virtue of their activities act as a subset of numerous cellular antioxidants defense systems against ROS species that are associated with many disease-causing electrophiles. [2,7,8] NADH-methaemoglobin reductase (NADH-MR) (EC: 1.6.2.2) transfers electrons from NADH + H + to cytochrome b 5 via its flavin adenine dinucleotide (FAD) prosthetic group. [9] This erythrocyte enzyme maintains hemoglobin in its ferrous (Fe 2+ ) state.…”

Glutathione S-Transferase Gene Polymorphisms and the Development of New-Onset Diabetes After Liver Transplant

“…Restriction fragment length polymorphism-polymerase chain reaction (PCR) and multiplex PCR methods were used to determine the genotype of the GST gene in each sample (Table 1). 26,27 restriction fragment length polymorphism and multiplex Pcr techniques GSTM1 and GSTT1 genetic polymorphisms were determined using a multiplex PCR technique. Polymerase chain reaction amplification for the GSTM1 and GSTT1 locus was performed using an initial denaturation step at 94°C for 2 minutes, followed by denaturation at 94°C for 2 minutes, annealing at 64°C for 1 minute, an extension step at 72°C for 1 minute in 35 cycles, and a final extension step at 72°C for 10 minutes.…”

“…The primers for the PCR studies are summarized in Table 1. 26,27 Statistical analyses Descriptive analyses were reported as frequencies. Quantitative variables were expressed as means ± standard deviation.…”