The Relation between Glutathione S Transferase (GSTM1, GSTP1 and GSTT1) Polymorphisms and Clinical Diversity of Sickle Cell Disease among Pediatric Sudanese Patients

Background: Sickle cell disease (SCD) is a highly variable condition, with some patients being asymptomatic and others frequently admitted to hospital. Impairment of the glutathione system due to genetic polymorphisms of glutathione S-transferase (GST) genes is expected to influence on the severity of SCD manifestations.

Objectives: This study aimed to investigate the possible association between the presence of GSTM1, GSTT1 and GSTP1 gene polymorphisms and SCD severity, diversity and complications.

Study Design: Cross-section hospital based 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 patients, 78 (61.9%) are males and 48 (38.1%) are female.

GSTM1 and GSTT1 genotypes were determined by polymerase chain reaction (PCR), GSTP1 genotyping was conducted with a PCR-RFLP, and the data analyzed by SPSS version 23.

Results: The GSTM1null genotype was found to be present in male more than female (OR=2.6 and p=0.002) and trend to be protective from development of Dactylitis (OR=0.313 and p=0.006) and reduce risk to develop ACS (OR=0.23 and p=0.002) while this polymorphism increase requirement for blood exchange (OR=1.1 and p=0.044), the GSTT1null genotype found to be present in female more than male (OR=2.6 and p=0.012) and this polymorphism reduce requirements for blood transfusion (OR=0. 137 and p< 0.001) and annual hospitalization (OR=0.436 and p=0.029), and reduce risk to development of stroke (OR=0.125 and p=0.008), polymorphism of both GSTM1 and GSTT1 found to be associated with appearance of disease before one year of age (OR=1.43 and p=0.004) and trend to be protective from development of Dactylitis (OR=0.124 and p=0.002),and there are no statistically significance association between GSTP1 gene polymorphism and gender variability and clinical manifestations of SCD.

Conclusion: Some GST genes polymorphisms were significantly associated with increased risk and some trend to have protective effect on clinical manifestations of SCD.