The Relation between Glutathione S Transferase (GSTM1, GSTP1 and GSTT1) Polymorphisms and Clinical Diversity of Sickle Cell Disease among Pediatric Sudanese Patients
Naif Taleb Ali *
Department of Hematology and Immunohematology, Faculty of Medical Laboratory Sciences, Gezira University, Sudan.
Ozaz Yagoup Mohammed Ahmed
Department of Hematology and Immunohematology, Faculty of Medical Laboratory Sciences, Gezira University, Sudan.
Fayad Osman Mohammed
Institute of Endemic Diseases, University of Khartoum, Khartoum, 11111, Sudan.
Huda Mohammed Haroun
Department of Hematology and Immunohematology, Faculty of Medical Laboratory Sciences, Gezira University, Sudan.
*Author to whom correspondence should be addressed.
Abstract
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.
Keywords: SCD, GST, GSTM1, GSTT1, polymorphisms, ACS, Sudan