Significant difference between the frequency of glutathione-S-transferase M1, glutathione-S-transferase T1 and glutathione-S-transferase P1 polymorphisms in type 1 diabetes patients and controls

Abstract

Background and Aim: Oxidative damage can lead cells to apoptosis which is believed to be the main cause of pancreatic β-cell death and eventually end up to the development of type 1 diabetes (T1D). Glutathione S-transferase enzymes (GSTs) play a crucial role in counteracting reactive oxygen species (ROS). In this study, we evaluated the association of three well-known polymorphisms of GSTM1, GSTT1 and GSTP1 in the pathogenesis of T1D which are whole gene deletions in GSTM1 and GSTT1 and a single nucleotide polymorphism (SNP) in GSTP1 known as Ile105Val. Materials and Methods: Samples were collected from 159 patients diagnosed with T1D and 210 control subjects. Genotyping for GSTM1 and GSTT1 was performed by Multiplex Polymerase Chain Reaction (PCR) and by PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) for GSTP1. Results: The GSTM1 and GSTT1 null genotypes were present at frequencies of 54 % and 59.1 % in T1D cases, whereas in controls the frequencies were 41.4 % and 43.3 %, respectively. Double-null genotype was found to be elevated among T1D patients (Odds Ratio [OR], 2.04; 95 % Confidence Interval [CI], 1.08-3.85; P = 0.027). No effect of any genotype for GSTP1 on T1D susceptibility was detected. Individuals with both the double-null and GSTP1 Ile/Val genotype combined appeared to be at increased risk of T1D (OR, 4.95; 95% CI, 2.11-11.6; P = 0.0002). Conclusion: This is the first study conducted on Iranian children with T1D. The absence of GSTM1 and/or GSTT1 may be important risk factor for T1D. Furthermore, presence of Val allele for GSTP1 could strengthen this risk.