Association of Glutathione S Transferase M1, T1, P1 (GSTM1, GSTT1, GSTP1) Gene Polymorphisms with Sickle Cell Anaemia Complications in North Kordofan State, Sudan

Abstract

Sickle cell anaemia (SCA) is an inherited blood disorder that is characterized by chronic haemolysis and episodes of many clinical complications. The number of people living with sickle cell disease globally increased from 5.46 million in 2000 to 7.74 million in 2021. This study aimed to investigate the association of glutathione S transferase M1, T1, P1 (GSTM1, GSTT1, GSTP1) gene polymorphisms with SCA complications. This was a case-control and hospital-based study, conducted in the SCA center, Alkuaiti Hospital, North Kordofan state, Sudan. Following informed consent, one hundred twenty-six participants were recruited to this study, 63 were SCA patients attending Alkuaiti Hospital, and 63 age and gender matched apparently healthy individuals as the control group. The full blood count was done using an automated hematological analyzer, genotyping of the GSTM1 and the GSTT1 polymorphisms were determined using multiplex polymerase chain reaction, while genotyping of the GSTP1 was determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Complications data were collected from admission and discharge records. 52.4% (n=33) from the case group were male and 47.6% (n=30) were females. The GSTM1 genotypes in the case group showed that the frequency of the GSTM1Null genotype was 57.1% and the GSTM1 present genotype was 42.9%, the GSTM1 genotypes in the control group showed that the frequency of the GSTM1Null genotype was 52.4% and the GSTM1 present genotype was 47.6%. The GSTT1 genotypes in the case group showed that the frequency of the GSTT1 Null genotype was 69.8%, and the GSTT1 present genotype was 30.2%. The GSTT1 genotypes in the control group showed that the frequency of the GSTT1 Null genotype was 49.8%, and the GSTT1 present genotype was 50.2%. The GSTM1 GSTT1 genotypes in the case group showed that the frequency of the GSTM1 GSTT1 Null genotype was 74.6%, and the GSTM1 GSTT1 present genotype was 25.4%. The GSTM1 GSTT1 genotypes in the control group showed that the frequency of the GSTM1 GSTT1 Null genotype was 77.7% and the GSTM1 GSTT1 present genotype was 22.3%. The GSTP1 genotype in the case group showed that the wild-type Ile/Ile was (15.9%), the heterozygous Ile/Val was (66.7%), and the homozygous mutant Val/Val was (17.4%). The GSTP1 genotype in the control group showed that the wild-type Ile/Ile was (3.2%), the heterozygous Ile/Val was (84.1%), and the homozygous mutant Val/Val was (12.7%). There were no statistically significant differences in the Hb, TWBCs, and PLTs between the GSTM1 genotypes (P.value =0.69, 0.47, 0.22) respectively also there were no statistically significant differences in the Hb, TWBCs, and PLTs between the GSTT1 genotypes (P.value = 0.84, 0.45, 0.48) respectively and the GSTM1 GSTT1 genotypes (P.value= 0.53, 0.70, 0.46) respectively. There were no statistically significant differences in the Hb, and TWBCs between the GSTP1 genotypes (P.value= 0.15, 0.36) respectively but there was a statistically significant difference in PLTs between the GSTP1 genotypes (P.value= 0.07). The study concluded that there were no statistically significant differences in the GSTM1 and the GSTM1 GSTT1 genotypes between the case group and the control group with (P.value= 0.36, 0.36) respectively and there were statistically significant differences in the GSTT1 and the GSTP1 genotypes between the case group and the control group with (P.value 0.014, 0.02) respectively. The GSTT1 present genotype was significantly associated with acute heart failure (P.value 0.02). The GSTP1 (val val) genotype was significantly associated with painful crisis and hepatomegaly as combined complications (P.value 0.008). The other GSTT1, other GSTP1, and GSTM1 genotypes revealed no significant associations with SCA complications.