444A Study of Genetic Polymorphism of GSTM1 and GSTT1 in Healthy Volunteers and Leukemic Patients

Abstract

Genetic polymorphism might be consider as a marker for predisposition of different diseases including leukemia. Glutathione S Transferase has role in metabolism of different types of Xenobiotics to facilitate their excretion from the body. It has also role in the metabolism of the drugs used in chemotherapy for different diseases. There are many genes that exhibit polymorphism but most of them show single nucleotide polymorphism. The deletion of whole gene is rare. GSTM1 and GSTT1 members of glutathione family are polymorphically deleted. Purpose of the study was to investigate deletion of these two isozymes in local Pakistani population and to investigate if any relationship exists in leukemic population. Male and females of healthy and leukemic patient volunteers were selected. Leukemic population was further divided into different groups (ALL, CLL, AML and CML). Biochemical parameters and oxidantion status of all patients and healthy volunteers were measured by kit method and Genetic polymorphism was seen by PCR and gel electrophoresis. Total bilirubin, creatinin, urea and ALT is greater in patients compared to healthy volunteers. Total oxidant status was low while total antioxidant status was high in healthy volunteers compared to patients depending on disease condition. Healthy subjects show 54% deletion of genes (66% and 52% in female and male respectively). Patients show 67% deletion of GSTM1 gene in which ALL 66% (68% and 76%, CLL 70% (80% and 60%), AML 70% (72% and 68%) and CML 62% (60% and 64%) in female and male respectively. GSTT1 deletion found healthy volunteers was 71% and it is 72% and 70% in female and male respectively and was found 70% in leukemic patients. ALL 78% (76% and 80%), CLL 76% (80% and 76%), AML 66% (76% and 76%) and CML 60% (56% and 64%) female and male respectively. All patients and healthy volunteers have more than 50% deletion of GSTM1 and GSTT1 genes. More deletion of GSTM1 was seen in patients than healthy volunteers while local population seems to be more prone to leukemia and may respond less to some chemotherapeutic drugs.