Republican Medical Genetic Consultation, Scientific Center of Obstetrics, Gynecology and Perinatology, 050020, 125 Dostyk Ave., Almaty, Kazakhstan.
Scientific Center of Pediatrics and Pediatric Surgery, 050060, 146 Al-Farabi Ave., Almaty, Kazakhstan.
Asian Pac J Cancer Prev. 2023 Aug 1;24(8):2653-2666. doi: 10.31557/APJCP.2023.24.8.2653.
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.
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.
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.
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.
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.
如今，急性淋巴细胞白血病是造血系统最常见的恶性疾病之一。各种不同种族人群中，急性淋巴细胞白血病的遗传易感性尚未得到充分探索。
本研究旨在对多态基因变异的等位基因和基因型的人群频率进行对比分析：免疫调节 GATA3(rs3824662)；B 细胞转录和分化：ARID5B(rs7089424、rs10740055)、IKZF1(rs4132601)；造血细胞分化：PIP4K2A(rs7088318)；细胞凋亡：CEBPE(rs2239633)、肿瘤抑制因子：CDKN2A(rs3731249)、TP53(rs1042522)；致癌物代谢：CBR3(rs1056892)、CYP1A1(rs104894、rs4646903)。这些基因变异与儿科 B 细胞急性淋巴细胞白血病（B-ALL）的发病风险相关，是基于全基因组关联研究分析的结果，研究对象为哈萨克族同一种族的人群。
本研究的基因组数据库包含了 1800 名条件健康的哈萨克族个体，他们的基因分型使用的是 deCODE genetics 公司的 OmniChip 2.5-8 Illumina 芯片，这是欧盟框架计划下的 InterPregGen 7 项目的一部分，项目由欧盟第 7 框架计划资助，协议号为 282540。
免疫调节基因 GATA3(rs3824662)的单核苷酸多态性（SNP）次要等位基因的人群频率较高，为 42.5%；B 细胞转录和分化基因 ARID5B(rs7089424)和 rs10740055)的人群频率分别为 33.1%和 48.5%，这表明它们对哈萨克族人群 B-ALL 发病风险和治疗效果有显著的遗传贡献。CBR3(rs1056892)基因 G 等位基因的人群频率明显较低，为 38.6%，这表明其在降低儿童 B-ALL 发病风险和减少蒽环类药物治疗后心脏并发症方面有显著的保护作用。
本研究结果将为开发有效的方法提供依据，用于预测儿童 B-ALL 的发病风险、早期诊断和治疗效果。
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