Preeclampsia is a serious complication of pregnancy, affecting both maternal and fetal health. In genome-wide association meta-analysis of European and Central Asian mothers, we identify sequence variants that associate with preeclampsia in the maternal genome atZNF831/20q13 andFTO/16q12. These are previously established variants for blood pressure (BP) and theFTOvariant has also been associated with body mass index (BMI). Further analysis of BP variants establishes that variants atMECOM/3q26,FGF5/4q21 andSH2B3/12q24 also associate with preeclampsia through the maternal genome. We further show that a polygenic risk score for hypertension associates with preeclampsia. However, comparison with gestational hypertension indicates that additional factors modify the risk of preeclampsia.

There are numerous scientific studies of recurrent miscarriage (RM) with possible causes, such as fetal chromosomal abnormalities, infectious agents, adverse environmental factors, bad habits, anatomical defects, thrombophilic disorders, etc. However, RM causes in 50% of cases remain unknown. These RM cases do not have any explainable etiology, and they require in-depth etiopathogenesis study, thus they are considered idiopathic RM. The purpose of this research is to study polymorphisms relationship of the immune response genes CX3CR1 (rs3732379, Val249Ile), CTLA4 (rs3087243, CT60 G/A), and HLA DQA1, DQB1, DRB1 (major histocompatibility complex, class II) with the idiopathic form of recurrent miscarriage (iRM) development in Kazakh population. Independent replicative TagMan genotyping for 302 patients with iRM and 300 women with normal reproduction was performed. It has been shown that carriage of unfavorable genotypes (Val/Ile, Val/Val) by the Val249Ile polymorphism of the CX3CR1 gene increases the risk of developing iRM by 1.43 times. Search for associations of genes allelic variants of HLA class 2 complex with iRM revealed *501 allele in DQA1 locus, *0301 in DQB1 locus, *10, *12, *15, *16 alleles in DRB1 locus, which increases the risk of developing iRM in Kazakh population with OR from 1.34 to 4.5. As a result of the study, obtained highly significant associations of immune response genes with the development of iRM in the Kazakh population indicate the possible involvement of the immune system interaction of mother cells with syncytiotrophoblast, which is realized by vascularization defects, defective embryo implantation, and leads to early pregnancies' termination.

Background: It seems that 50% of the possible causes of recurrent miscarriage do not have any explainable etiology and they require in-depth etiopathogenesis analysis. The purpose of this research was to study polymorphisms relationship of the im-mune response genes including Val249Ile CX3CR1 (rs3732379), CT60 G/A CTLA4 (rs3087243), and HLA DQA1, DQB1, DRB1 (major histocompatibility complex, class II) with development of idiopathic form of recurrent miscarriage (iRM) in Kazakh population. Methods: TagMan genotyping for 302 patients with iRM and 300 women with normal reproduction was performed. Molecular genetic studies were carried out by the TaqMan method of unified site-specific amplification and real-time genotyping using test systems. Statistical tests and Chi Square were carried out using PLINK, STATA13 software and p˂0.05 was considered statistically significant. Results: It has been shown that carriage of unfavorable genotypes (Val/Ile, Val/Val) by the Val249Ile polymorphism of CX3CR1 gene increases the risk of developing iRM by 1.43 times. Search for associations of genes allelic variants of HLA class 2 complex with iRM revealed 501 allele in DQA1 locus, 0301 in DQB1 locus, 10, 12, 15, 16 alleles in DRB1 locus, which increase the risk of developing iRM in Kazakh population. Conclusion: The highly significant associations of immune response genes with development of iRM in Kazakh population indicate the possible involvement of the immune system interaction of mother cells with syncytiotrophoblast, which is realized by vascular defects and defective embryo implantation, causing termination of pregnancy.

Objective: Breast cancer is the most common form of cancer in women in the world with more than 400,000 deaths each year worldwide. The aim of this study is to compare population frequencies of alleles and genotypes of polymorphic variants of BRCA1 and BRCA2 genes associated with breast cancer risk in an ethnically homogenous Kazakh population with previously studied world populations. The material of the study was DNA isolated from peripheral blood of the enrolled population control group, represented by 1800 conditionally healthy individuals of Kazakh ethnicity. Methods: The DNA extraction was possible with the use of M-PVA magnetic particle separation method on the Prepito (PerkinElmer) automatic analyser for extraction of Chemagic Prepito (Wallac, Finland) nucleic acids using the PrepitoDNACytoPure reagent kit. Statistical calculations of allele and genotype frequencies, significance tests, and non-parametric χ2 analysis were carried out using PLINK software. Results: The results favour for the high genetic heterogeneity of the studied polymorphisms, which reflects the specifics of the Kazakh population structure resulted from complex evolutionary and migration processes, as well as the median geographic location between the populations of Asia and Europe. Conclusion: Knowledge of the spectrum and frequency of mutations in BRCA1 and BRCA2 genes predisposing to breast cancer, which are present in varying frequencies in the Kazakh population, will provide a more effective approach to the screening protocol and allow for a faster, less expensive and more accessible genetic testing strategy for the Kazakhstan citizens.