Prevalence of Glutathione S Transferase (GSTM1, GSTP1 and GSTT1) Genes Polymorphisms among Pediatric Sudanese Patients with Sickle Cell Anemia

Abstract

Background: Sickle cell disease (SCD) is taken into account as one of the foremost types of anemia in Sudan, particulary in the western part of the country. The glutathione system plays a vital role in the removal of endogenous products of peroxidation of lipids, thus protecting cells and tissue against damage from oxidative stress. Impairment of the glutathione system as result of genetic polymorphisms of glutathione S-transferase (GST) genes is anticipated to increase the severity of SCD manifestations. Aims/Objectives: This study was aimed to evaluate the rate of GSTM1, GSTT1 and GSTP1 gene polymorphisms among sickle cell anemia pediatric patients in Sudan. Study Design: Case control study. Place and Duration of Study: This study carried out in Khartoum town in Jafar Ibn Auf Pediatric Hospital / Khartoum during the period (June 2017 to June 2020). Methodology: The total subjects of the confirmed diagnosis were 126 and 126 control. Among these cases of SCA 78 (61.9%) are males and 48 (38.1%) are female and for control 80 (63.5%) are male and 46 (36.5%) are female. We measured the frequency distribution of the three GSTs gene polymorphisms, GSTM1 and GSTT1 genotypes were determined by polymerase chain reaction (PCR). GSTP1 genotyping was conducted with a PCR-restriction fragment length polymorphism assay, SPSS version 23 was used to analyze the data. Results: The GSTM1 null genotype frequency was found to be slightly lower in the control group, (30.2% as opposed to 33.3% in SCA patients), but this difference was not considered to be statistically significant (OR = 1.16, 95% CI: 0.68-1.97; p- value = 0.5884), GSTT1 was found in 47.6% of SCA patients and 77.8% of the Control but the frequency of individuals carrying the GSTT1 null genotype was significantly higher among SCA patients, 52.4% compared to 22.2% of the Control; (OR = 3.85, 95% CI: 2.23- 6.65; p-value =0.0001). Individuals with a combined GSTM1 null/GSTT1 null genotype had an estimated 11.7-fold increased risk of SCA (OR=11.7; CI=2.67-51.2; p-value=0.0011). The homozygous mutant type (Val/Val) of GSTP1 showed significant difference between patients and controls (OR= 6.53, 95% CI: 1.41-30.24; P-value = 0.0164). Conclusion: The GSTT1 polymorphism and combined form of GSTM1 null/GSTT1 null genotype and the homozygous mutant type (Val/Val) of GSTP1 increase the risk of sickle cell anemia.