Glutathione S-Transferase Gene Polymorphisms (GSTM1, GSTT1, and GSTP1) in Egyptian Pediatric Patients with Sickle Cell Disease

Abstract

Sickle cell disease (SCD) complications are associated with oxidative stress. Glutathione S-transferases (GSTs) are a group of enzymes that protect against oxidative stress. The aims of this study was to evaluate the prevalence of GSTM1, GSTT1, and GSTP1 gene polymorphisms among homozygous sickle cell anemia patients and to investigate the possible association between the presence of these polymorphisms and SCD severity and complications. Genotyping the polymorphisms in GSTT1 and GSTM1 genes was performed using the multiplex polymerase chain reaction (PCR) method. The GSTP1 ILe105Val polymorphism was determined using PCR-restriction fragment length polymorphism. GSTM1 null genotype was significantly associated with increased risk of severe vaso-occlusive crises (VOC) (odds ratio = 1.52, 95% confidence interval = 0.42-5.56, P = 0.005). We found no significant association between GST genotypes and frequency of sickle cell-related pain, transfusion frequency, disease severity, or hydroxyurea treatment. GSTM1 gene polymorphism may be associated with risk of severe VOC among Egyptian SCD patients.

Evaluation of Glutathione-S-Transferase P1 Polymorphism and Its Relation to Bone Mineral Density in Egyptian Children and Adolescents With Beta- Thalassemia Major

“… 30 However, similar allele frequencies and genotype distribution of this polymorphism were found in 50 Egyptian SCA patients and healthy controls in another study. 31 Higher frequency of 105Val polymorphism among β-thalassemia patients detected in this work and among SCA patients in the previous Brazilian study 30 compared to the healthy controls may suggest genetic linkage between, GSTP1 gene (11q13) and β-globin gene (11p15).…”

Research Article <i>GSTT1</i> null genotype in sickle cell anemia and blood transfusion recurrence – a case report

“…reported the association of the null GSTT1 genotype with an increased need for blood transfusions. However, Shiba et al (2014) did not find that association. also reported the association between the GSTT1 polymorphism and acute thoracic syndrome and vaso-occlusion crises.…”

“…also reported the association between the GSTT1 polymorphism and acute thoracic syndrome and vaso-occlusion crises. Shiba et al (2014) reported that the complications related to SCA are associated with the intense process of oxidative stress, and the GST enzymes protect the body from oxidative stress. They found no significant association between the null genotypes and the frequencies of pain related to SCA, blood transfusion, disease severity or treatment with hydroxyurea.…”

GSTT1(rs4025935) null genotype is associated with increased risk of sickle cell disease in the populations of Tabuk—Northwestern region of Saudi Arabia

“…Several epidemiological studies have reported that the GSTT1 null genotypes results in a lack of functional protein which may cause increased vulnerability to oxidative DNA damage and excessive ROS generation and may ultimately result in increased susceptibility to various diseases associated with oxidative stress including SCD. 22 The distribution of GSTM1 and GSTT1 null genotypes varies among different ethnic groups. Several population-based studies have reported a prevalence ranging from 47 to 58% for the GSTM1 null genotype and from 13 to 25% for the GSTT1 null genotype among white Europeans 23 and 27.6% among the US white population.…”