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

Hematology. 2017 Apr;22(3):172-177. doi: 10.1080/10245332.2016.1201631. Epub 2016 Nov 25.


Background: Glutathione system plays an important role in the protection of cells and tissue against damage from oxidative stress. Impairment of the glutathione system due to genetic polymorphism of GST genes may increase the risk and severity of sickle cell disease (SCD). Present study was, therefore, undertaken to examine the relative impact of the genetic polymorphism of GSTT1 and GSTM1 (rs4025935 and rs71748309) on susceptibility and hematological aspects of the patients with SCD.

Methods: Present study included 100 patients with SCD and 200 healthy controls from northwestern region of Saudi Arabia. GSTM1 and GSTT1 (rs4025935 and rs71748309) genotypes were investigated by using single-tube multiplex PCR technique.

Results: It was observed that patients with SCD possessed significantly higher frequency of GSTT1 null genotype (26%) than healthy controls (15%), (P = 0.00001). Compared to the presence of GSTT1 genotype, the OR for the GSTT1 null genotype were estimated to be 4.3 (2.17-8.64, P = 0.00001). However, such association was not observed with respect to the presence of GSTM1 null genotype. In addition, it was observed that SCD in patients with GSTT1 genotype, the mean percentage levels for HbF and HbS were 0.48 and 35.4%, respectively; however, among SCD patients with GSTT1 null genotype, the mean percentage levels were significantly higher 1.62% (P = 0.004) and 39.38% (P = 0.02), respectively.

Conclusion: GSTT1 null genotype is significantly associated with increased risk of SCD among the population of northwestern region of Saudi Arabia. In addition, it may be one of the important factors responsible for hematological manifestations of SCD.

Keywords: GSTT1 null and GSTM1 null genotypes; Null genotype; ROS; Sickle cell disease.

MeSH terms

  • Adult
  • Alleles
  • Anemia, Sickle Cell / diagnosis
  • Anemia, Sickle Cell / epidemiology*
  • Anemia, Sickle Cell / genetics*
  • Case-Control Studies
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Genotype*
  • Glutathione Transferase / genetics*
  • Humans
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Genetic
  • Population Surveillance
  • Risk
  • Saudi Arabia / epidemiology
  • Young Adult


  • glutathione S-transferase T1
  • Glutathione Transferase
  • glutathione S-transferase M1