Glutathione-S-transferase gene polymorphisms in children with acute lymphoblastic leukemia in the East Siberian Region
Authors:   Irkutsk State Medical University, Irkutsk, Russian Federation, S'emshchikova Yu.P. ,   Irkutsk State Regional Children's Clinical Hospital, Irkutsk, Russian Federation, Stepanenko L.A. ,   Irkutsk State Medical University, Irkutsk, Russian Federation, Peretolchina N.P. ,   Irkutsk State Medical University, Irkutsk, Russian Federation, Bokova T.A. ,   M.F. Vladimirskiy Moscow Regional Research and Clinical Institute, Moscow, Russian Federation,   Pirogov Russian National Research Medical University, Moscow, Russian Federation, Barzunova T.V. ,   Irkutsk State Medical University, Irkutsk, Russian Federation, Kozlov Yu.A. ,   Irkutsk State Medical University, Irkutsk, Russian Federation,   Irkutsk State Regional Children's Clinical Hospital, Irkutsk, Russian Federation, Malov S.I. ,   Irkutsk State Medical University, Irkutsk, Russian Federation, Tolmacheva O.P. ,   Irkutsk State Regional Children's Clinical Hospital, Irkutsk, Russian Federation, Umnova S.Yu. ,   Irkutsk State Regional Children's Clinical Hospital, Irkutsk, Russian Federation, Bilyak Yu.S. ,   Irkutsk State Regional Children's Clinical Hospital, Irkutsk, Russian Federation, Ovanesyan S.V. ,   Irkutsk State Regional Children's Clinical Hospital, Irkutsk, Russian Federation, Malov I.V. ,   Irkutsk State Medical University, Irkutsk, Russian Federation
Published: January 2025

Background: glutathione S-transferase (GST) is one of phase II xenobiotic metabolizing enzymes. Enzyme gene site deletions (‘'null'' genotype)
lead to a decrease in enzyme expression and activity. This is associated with both the disease course features and risks of their occurrence.
Aim: to study the features of GSTT1, GSTM1 genetic polymorphisms in children in the East Siberian Region and their possible association
with acute lymphoblastic leukemia.
Materials and Methods: 82 children with acute lymphoblastic leukemia and 227 healthy students of medical colleges without a history of
oncohematological conditions were examined. All of them belonged to the Russian ethnic group. Average age was 5.59±4.57 and 19.6±1.6
years in leukemia patients and controls, respectively. Deletion polymorphisms in human glutathione S-transferase genes (GSTT1 and GSTM1)
was detected by polymerase chain reaction (PCR) with agarose gel electrophoresis of PCR amplification products. PCR samples represented
DNA samples isolated from buccal epithelium samples.
Results: functionally active GSTT1 genotype frequency is predominant both in leukemia patients and healthy controls (82.93% and 80.18%,
respectively). GSTT1 deletion is rare (17.07% vs. 19.82% in leukemia patients and controls, respectively). Functionally active and deletion alleles
of GSTM1 are equally common in both groups. In particular, GSTM1-active frequency is 46.34% and 50.66% in leukemia patients and healthy
subjects, respectively. As for GSTM1 deletion, the frequency is 53.66% and 49.34% in leukemia patients and controls, respectively. When
calculating the odds ratio for pediatric acute leukemia, depending on GSTT1 and GSTM1 gene deletions, no significant differences were found
(p>0.05, chi-square method). The analysis of combinations of homozygous deletions in the GSTT1 and GSTM1 genes according to the Fisher's
exact test revealed no differences between acute leukemia patients and healthy subjects. The comparative distribution frequency of functional and
null GSTT1 and GSTM1 genotypes between ethnic Russians of Eastern Siberia and global populations demonstrated significant differences for
the null GSTT1 genotype only (19.8% vs. 48% for Eastern Siberian population and that of Eastern Asia, respectively) (χ2=70.21, df=1, p<0.001).
Conclusions: the functional GSTT1 genotype prevails in the Caucasian ethnic group in the East Siberian Region; the GSTM1 gene deletions
are equally common in healthy subjects and children with acute lymphoblastic leukemia. GSTM1 and GSTT1 gene deletions are not associated
with a risk of acute lymphoblastic leukemia in children of the Caucasian ethnic group in the East Siberian Region.
KEYWORDS: glutathione-S-transferase, GSTT1, GSTM1, single-nucleotide polymorphisms, xenobiotics, children, hemoblastoses,
lymphoblastic leukemia, pharmacogenetics, personalised medicine.
FOR CITATION: S'emshchikova Yu.P., Stepanenko L.A., Peretolchina N.P., Bokova T.A., Barzunova T.V., Kozlov Yu.A., Malov S.I., Tolmacheva
O.P., Umnova S.Yu., Bilyak Yu.S., Ovanesyan S.V., Malov I.V. Glutathione-S-transferase gene polymorphisms in children with acute
lymphoblastic leukemia in the East Siberian Region. Russian Journal of Woman and Child Health. 2024;7(4):323–329 (in Russ.). DOI:
10.32364/2618-8430-2024-7-4-5