Genetic Markers of Acute Childhood B-Lineage Lymphoblastic Leukemia in the Kazakh Population.

INTRODUCTION: To investigate the genetic contribution of 24 GWAS-associated polymorphic gene variants on the development of children's B-lineage acute lymphoblastic leukemia (B-ALL) in an ethnically homogeneous population of Kazakhs. METHODS: A study of 205 children with B-ALL and 204 healthy children was conducted. Genotyping of polymorphic loci was carried out using the TaqMan method. RESULTS: Significant associations (p < 0.05) with the risk of childhood B-ALL were found for twelve variants, including rs6457327 of the HLA gene, rs4251961 of the IL1RN gene, and rs1800630 of the TNF gene. Carriage of the minor allele A of the protective rs1801157 polymorphism A of the CXCL12 gene reduces the risk of B-ALL in the Kazakh population by 40%. DISCUSSION: The results reveal significant associations of polymorphic genetic variants, which can serve as a basis for the development of effective methods for predicting the risk of B-ALL, early diagnosis, and timely treatment.

Genes of Inflammation and Placental Function GWAS Associated with Idiopathic Recurrent Miscarriage in the Kazakh Population.

Background: The loss of two or more pregnancies is considered recurrent miscarriage (RM). One of the causes of this pathology is the occurrence of mutations both in pleiotropic and pathway-specific regulators and in structural genes. The simplest type of such mutations is single nucleotide polymorphisms. Aims: The aim of the study is to study the relationship between gene polymorphisms of anti- and pro-inflammatory cytokines - interferon-gamma (T874A), interleukin (IL1B) (C3954T), IL6 (G572C) and IL10 (G1082A); placental function, apoptosis and angiogenesis - apolipoprotein C-III (APOC3) (G5163C), kinase insert domain receptor (A1719T, G1192A), P53 (Arg72Pro) and signal transducer and activator of transcription 3 (STAT3) (C1697G) with the development of idiopathic RM (iRM) in the Kazakh population. Settings and Design: This was a case-control study. Materials and Methods: Molecular genetic studies were performed by TaqMan using a single site-specific amplification and real-time genotyping method in 302 women with iRM and 300 with normal reproduction. DNA isolation from the biomaterial was carried out using kits containing binding magnetic particles. Both samples were analysed for alleles and genotypes for the studied polymorphisms. Statistical Analysis Used: For statistical data processing, Pearson's criterion, confidence interval (CI) and probability value were taken into account. Results: It was found that the carriage of unfavourable genotypes (G/C, C/C) for the G5163C polymorphism of the APOC3 gene increases the risk of developing iRM by three times (odds ratio = 3.0; 95% CI = 2.24-4.07). Other studied polymorphisms in the genes of ILs, interferon, P53 proapoptotic protein, kinase domain receptor and STAT3 transcription activator were not associated with RM. Conclusion: Significant associations of APOC3 gene genotypes with the development of iRM in the Kazakh population indicate the involvement of the placental system, which is realised by vascularisation defects and defective embryo implantation and leads to early pregnancy termination.