Background. Glutamate cysteine ligase (GCL) is a rate-limiting enzyme in synthesis of glutathione. Evidence suggests that genetic variations in the promoter region of genes coding a catalytic subunit (GCLC -129T/C) and a modifier subunit (GCLM -588C/T) of GCL have a functional impact on their transcriptional activity and were associated with various disorders. Hence, we hypothesize whether these two polymorphic variants of GCLM and GCLC genes are associated with the risk of ischemic heart disease (IHD) development in the population of Kazakhstan. Methods. We evaluated 360 patients with IHD and 341 control subjects. Allele frequencies of studied promoters’ polymorphisms were detected by PCR-RFLP analysis. Multiple logistic regression analysis was applied to assess the risk for different genotypes obtained. Results. The presence of -588T allele in GCLM and -129T allele in GCLC gene genotypes was associated with an increased risk of IHD (GCLM -588T: OR=3.92, p=0.003; GCLC -129T: OR=3.22, p=0.03) for general ethnically mixed group. Analysis of each ethnical groups separately showed the higher risk tendency for Kazakhs as for GCLM -588T (OR=4.79; p=0.03) and as for GCLC -129T (OR=4.79, p=0.03). For Russians, statistically differences for two polymorphisms were not observed. Conclusion. The two promoter polymorphisms of GCLM (-588C/T) and GCLC (-128T/C) are associated with an increased risk of IHD in Kazakhstan population.

The association of genetic polymorphisms with the individual sensitivity of humans to the action of pesticide pollution is being actively studied in the world. The aim of this study was a molecular epidemiological analysis of candidate polymorphisms of genes involved in pesticide metabolism, detoxification, and antioxidant protection. Some of the selected polymorphisms also relate to susceptibility to cancer and cardiovascular, respiratory, and immune system diseases in individuals exposed to pesticides for a long time. For a case-control study of a unique cohort of people exposed to organochlorine pesticides for 10 years or more were chosen, a control cohort was selected that matched with the experimental group by the main population characteristics. PCR-PRLF and genome-wide microarray genotyping (GWAS) methods were used. We identified 17 polymorphisms of xenobiotic detoxification genes and 27 polymorphisms of antioxidant defense genes, which had a significantly high statistical association with the negative impact of chronic pesticide intoxication on human health. We also found 17 polymorphisms of xenobiotic detoxification genes and 12 polymorphisms of antioxidant defense genes that have a protective effect. Data obtained added to the list of potential polymorphisms that define a group at high risk or resistant to the negative effects of pesticides.

Autism spectrum disorders (ASDs) are heterogeneous diseases that are triggered by a number of environmental and genetic factors. The aim of the current study was to investigate an association of the rs1799836 genetic variant of the neurotransmitter-related gene MAOB with ASDs. In total, 262 patients diagnosed with ASDs and their 126 healthy siblings were included in the present study. All individuals represented a Kazakhstani population. The distributions of the rs1799836 genotype were in accordance with the Hardy-Weinberg equilibrium among both cases and controls. No statistically significant differences were found in the allelic distributions of this polymorphism between ASD and control subjects (A/G: for males OR=1.11, 95% 0.59-2.06, p=0.75; for females OR=1.14, 95% 0.70-1.86, p=0.76). However, the increased score in the overall CARS was significantly associated with the A allele of rs1799836 MAOB for females (OR=2.31, 95% 1.06-5.04, p=0.03). The obtained results suggest that the rs1799836 polymorphism of the MAOB gene may have little contribution to the development of ASDs but may be involved in pathways contributing to ASD symptom severity in females. Further large-scale investigations are required to uncover possible relationships between rs1799836 MAOB and ASD progression in a gender-specific manner and their possible application as a therapeutic target.

The study of extended pedigrees containing autism spectrum disorder- (ASD-) related broader autism phenotypes (BAP) offers a promising approach to the search for ASD candidate variants. Here, a total of 650,000 genetic markers were tested in four Kazakhstani multiplex families with ASD and BAP to obtain data on de novo mutations (DNMs), common, and rare inherited variants that may contribute to the genetic risk for developing autistic traits. The variants were analyzed in the context of gene networks and pathways. Several previously well-described enriched pathways were identified, including ion channel activity, regulation of synaptic function, and membrane depolarization. Perhaps these pathways are crucial not only for the development of ASD but also for . The results also point to several additional biological pathways (circadian entrainment, NCAM and BTN family interactions, and interaction between L1 and Ankyrins) and hub genes (CFTR, NOD2, PPP2R2B, and TTR). The obtained results suggest that further exploration of PPI networks combining ASD and BAP risk genes can be used to identify novel or overlooked ASD molecular mechanisms.

Breast cancer is a global health problem. It is an age-dependent disease, but cases of early-onset breast cancer (eBC) are gradually increasing. There are many unresolved questions regarding eBC risk factors, mechanisms of development and screening. Only 10% of eBC cases are due to mutations in the BRCA1/BRCA2 genes, and 90% have a more complex genetic background. This poses a significant challenge to timely cancer detection in young women and highlights the need for research and awareness. Therefore, identifying genetic risk factors for eBC is essential to solving these problems. This study represents an association analysis of 144 eBC cases and 163 control participants to identify genetic markers associated with eBC risks in Kazakh women. We performed a two-stage approach in association analysis to assess genetic predisposition to eBC. First-stage genome-wide association analysis revealed two risk intronic loci in the CHI3L2 gene (p = 5.2 × 10⁻⁶) and MGAT5 gene (p = 8.4 × 10⁻⁶). Second-stage exonic polymorphisms haplotype analysis showed significant risks for seven haplotypes (p < 9.4 × 10⁻⁴). These results point to the importance of studying medium- and low-penetrant genetic markers in their haplotype combinations for a detailed understanding of the role of detected genetic markers in eBC development and prediction.

Modern approaches to reproductive biotechnology include the development of effective methods for long-term storage of gametes and reproductive tissues of animals. One of the promising areas is cryopreservation of ovarian tissue, which allows preserving fertility, especially in rare and valuable species. However, the effectiveness of this technology directly depends on the type of cryoprotectant, freezing mode, cooling rate and storage method. Nonequilibrium cryopreservation is a method in which biological samples are exposed to liquid nitrogen vapor without strict software control of cooling. This approach allows for a simpler procedure but requires careful optimization of conditions to preserve tissue viability. The aim of this work is to evaluate the effect of various cryoprotectants and the altitude of the samples (4, 5 and 6 cm above the surface of liquid nitrogen) on the morphological preservation of follicles in the ovarian tissue of dogs after nonequilibrium cryopreservation. A study was conducted to investigate the effect of nonequilibrium cryopreservation in liquid nitrogen vapor on the morphofunctional state of ovarian tissue in dogs. Four cryoprotectors (dimethyl sulfoxide, ethylene glycol, propylene glycol, glycerol) and three temperature regimes (4 cm, 5 cm and 6 cm from the liquid nitrogen level) were used. After thawing, a histological analysis was performed to assess the degree of preservation of different types of follicles. It was found that the best viability indicators were observed when using 1.5 M dimethyl sulfoxide (4 and 6 cm), glycerol (4 cm) and propylene glycol (5 cm). The data obtained are important for the development of effective protocols for cryopreservation of ovarian tissue in dogs in order to preserve the gene pool and reproductive potential.