Background: Today, acute lymphoblastic leukemia is one of the most common malignant diseases of the hematopoietic system. The genetic predisposition to ALL is not fully explored in various ethnic populations.
Objective: The study aimed to conduct a comparative analysis of the population frequencies of alleles and genotypes of polymorphic gene variants: immune regulation GATA3 (rs3824662); transcription and differentiation of B cells: ARID5B (rs7089424, rs10740055), IKZF1 (rs4132601); differentiation of hematopoietic cells: PIP4K2A (rs7088318); apoptosis: CEBPE (rs2239633), tumor suppressors: CDKN2A (rs3731249), TP53 (rs1042522); carcinogen metabolism: CBR3 (rs1056892), CYP1A1 (rs104894, rs4646903), according to genome-wide association studies analyses associated with the risk of developing pediatric beta-cell acute lymphoblastic leukemia (B-cell ALL), in an ethnically homogeneous population of Kazakhs with studied populations.
Methods: The genomic database consists of 1800 conditionally healthy persons of Kazakh nationality, genotyped using OmniChip 2.5-8 Illumina chips at the deCODE genetics as part of the InterPregGen 7 project of the European Union (EU) framework program under Grant Agreement No. 282540.
Results: High population frequencies of single nucleotide polymorphism (SNP) minor alleles identified for immune regulation genes - GATA3 rs3824662 - 42.5%; transcription and differentiation of B-cells genes - ARID5B rs7089424 - 33.1% and rs10740055 - 48.5%, which suggests their significant genetic contribution to the risk of development and prognosis of the effectiveness of B-cell ALL therapy in the Kazakh population. The significantly lower population frequency of the minor allele G rs1056892 CBR3 gene - 38.6% in the Kazakhs suggests its significant protective effect in reducing the risk of childhood B-cell ALL and the smaller number of cardiac complications after anthracycline therapy.
Conclusion: The obtained results will serve as a basis for developing effective methods for predicting the risk of development, early diagnosis, and effectiveness of treatment of B-cell ALL in children.
Keywords: B-cell lymphoblastic leukemia in children; SNP; genome; minor alleles; wide association studies analysis.