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The aim of the study was to develop a panel for detecting heterozygous carriage of frequent mutations associated with phenylketonuria (PKU), and to determine their allelic frequencies in one of the regions of Russia. PKU is one of the most common monogenic diseases with autosomal recessive inheritance. Carrier screening leads to a reduction in the number of children born with PKU. The diagnostic panel included 23 pathogenic variants of the PAH gene nucleotide sequence. Participants of the study (n = 642) were randomly selected from an ESSE-Vologda population-based study. Genotyping was performed using real-time polymerase chain reaction on a QuantStudio 12K Flex Real-Time PCR System (Thermo Fisher Scientific, United States). The data were analyzed using the TaqMan Genotyper Software (Thermo Fisher Scientific, United States). Seventeen heterozygous carriers of six variants of the nucleotide sequence associated with the development of PKU were identified: R408W (rs5030858), A403V (rs5030857), I306V (rs62642934), L48S (rs5030841), IVS12+1G>A (rs5030861), R261Q (rs5030849_C_T). The frequency of heterogyzotes in the Russian population was 2.65% (95% CI 1.55–4.21), or 1 : 38. The data obtained indicate the prospects of mass screening for the carriage of frequent mutations associated with PKU in people with an uncomplicated family history. The developed diagnostic panel allows one to rapidly obtain the result of genetic analysis and can be used for PKU carrier screening.

Parkinson’s disease (PD) is one of the most common neurodegenerative pathologies. This disorder is associated with death of predominantly dopaminergic neurons. A characteristic feature of PD is a long latent period of disease development, which makes it impossible to investigate and diagnose PD at the earliest clinical stages. One of the approaches to solving this problem is the examination of the peripheral blood of untreated PD patients at the early clinical stages. Changes in relative mRNA levels of genes in peripheral blood can be considered as potential biomarkers at the early stages of PD. In this study, we analyzed changes in relative mRNA levels of genes CLN3, GABBR1, and WFS1 in peripheral blood in treated and untreated PD patients and in comparison groups using RT-qPCR with TaqMan probes. All the known functions of the proteins of the studied genes, as well as the identified associations of these genes with various neurological diseases, may indicate their possible involvement in PD pathogenesis. However, no statistically significant changes in mRNA levels in PD patients relative to the control were shown for any gene. No significant changes in relative mRNA levels in the neurological control group were shown either. So, the data presented in this paper suggest that genes CLN3, GABBR1, and WFS1 do not contribute to the pathogenesis of the disease, at least at the mRNA level, at the early symptomatic stages in patients with PD and, therefore, cannot be considered as biomarkers of the early stages of PD.

Currently, a number of peptide pharmaceuticals are widely used in medical practice, but the market size of such drugs remains relatively small. However, in the coming years, one can expect a significant increase in interest in peptide pharmaceuticals, which is primarily due to their low toxicity and wide range of possible molecular targets. The results obtained in recent years allow us to take a new approach to the development of such drugs, which will make it possible to expand the range of possible applications of peptide drugs and improve their efficiency and usability.

Circadian rhythms play an important role in the regulation of body metabolism, since the most important biochemical and physiological processes in the body are subjected to diurnal fluctuations. The transcription factor PERIOD3 encoded by the PER3 gene is one of the key components of the circadian negative transcription loop and, upon interaction with other proteins, affects the activity of the circadian clock. We aimed at studying genotype and allele frequencies of rs10462021 in the PER3 gene between the controls (N = 259) and different clinical types of depressive disorder, namely, depressive disorder (F32.1, 41.2) (N = 208) and recurrent depressive disorder (F 33.1) (N = 150), as well as patients with a history of suicide attempts (N = 100). No significant differences in distributions of genotype or allele frequencies between the groups were detected (p > 0.05). Therefore, there was no significant contribution of rs10462021 in the PER3 gene in the development of depressive disorder or various clinical types of depression.

We performed comparative analysis of associations between the F2 gene G20210A polymorphism, the F5 gene G1691A polymorphism, the GP1BA gene -5T/C polymorphism, the ACE gene insertion/deletion (I/D) polymorphism and the risk of developing stroke in two samples drawn from ethnic Russian and ethnic Ukrainian populations. It has been shown, that among the Russian population, the risk of developing ischemic stroke is increased in DD genotype individuals (odds ratio (OR) = 1.4, 95% confidence interval (CI) [1.05; 1.78], p = 0.02), whereas the I/I and I/D genotypes are associated with a decreased risk of developing stroke (OR = 0.7, 95% CI [0.56; 0.95], p = 0.02). In the ethnic Ukrainian sample, differences in the distribution of genotypes and allele frequencies between stroke patients and the control group of subjects with regard to this polymorphic locus are statistically unreliable and the ACE gene I/D polymorphism is unassociated with the risk of developing stroke in the Ukrainian population (OR = 0.8, 95% DI[0.48; 1.32], p = 0.45). The F2 gene G20210A polymorphism, the F5 gene G1691A polymorphism, and the GP1BA gene -5T/C polymorphism are unassociated with stroke risk factor across both ethnic samples.