Polymorphic Variants Of Genes Research Articles

Evaluation of the role of polymorphic variants of lipid metabolism-related genes in acne pathogenesis

Evaluation of the role of polymorphic variants of lipid metabolism-related genes in acne pathogenesis

The Role of rs2238296 of the Mitochondrial DNA Polymerase Gamma Gene in Combination with Polymorphic Variants of Antioxidant Defense Genes in the Development of Postinfarction Left Ventricular Aneurysm

The Role of rs2238296 of the Mitochondrial DNA Polymerase Gamma Gene in Combination with Polymorphic Variants of Antioxidant Defense Genes in the Development of Postinfarction Left Ventricular Aneurysm

Selection of Informative Genetic Markers for Assessment of Adaptabilities of Northerners: A Review

Introduction: Habitation and the process of adaptation of the population of northern regions to the harsh environment are associated with the development of such syndromes and conditions as polar tension, polar dyspnea, the polar metabolic type, premature aging, and north-related hypertension, and aimed at maintaining homeostasis constancy to ensure full life activity in extreme environmental conditions, it which issues of preserving human health and labor potential remain highly relevant. Objective: To review published data on physiological and genetic adaptation to adverse climate and environmental stressors and to establish informative genetic markers for assessing adaptabilities of northerners. Materials and methods: The review includes data of Russian and foreign studies published in Russian and English languages in 1980–2021 and cited in the Pubmed, NCBI, eLIBRARY.RU, Scopus, Web of Science, and RSCI databases. Of 330 articles found, 40 full-text materials were selected for this review based on the following criteria: availability of data on polymorphic variants of genes involved in the genetic adaptation of humans to extreme conditions of the north; availability of data on epidemiology of genes associated with multifactorial diseases most common in the circumpolar zone; availability of data on adverse health effects of environmental factors in northerners, and ethnic features of gene pools of indigenous people and newcomers of the circumpolar zone. Methods of information analysis were applied to summarize the results of studies reviewed. Results: A strategy for assessing the level of functional reorganization of the human organism in the North is proposed. The article also describes a panel of informative genetic markers selected for a comprehensive assessment of adaptability of northerners, including, inter alia, normal genetic variability of adapting people, with the purpose of creating region-oriented diagnostic maps allowing assessment of total risks of cold-related illnesses for timely correction of the lifestyle and taking preventive and therapeutic measures. Discussion: In the genetic and epidemiological study of human populations living in extreme environments, it is expedient to use a comprehensive approach that includes personalized, preventive and predictive assessment of medical, psycho-physiological and genetic determinants of the functional state matrix, reflecting the current level of adaptation of northerners.

The role of FADS gene polymorphic variants in adaptation to the Northern climatic conditions and metabolic disorders

The role of FADS gene polymorphic variants in adaptation to the Northern climatic conditions and metabolic disorders

Haplotype of CaSR gene is associated with risk of renal stone disease in West Indian population.

Calcium is the most abundant metabolite involved in the stone matrix. The CaSR gene controls calcium homeostasis, and genetic variation in the CaSR gene could lead to the development of renal stone disease. Therefore, the current study has been designed to assess the association of genetic variants of CaSR gene polymorphisms with renal stone disease. A single-centric prospective study has been carried out on a total of 300 participants (150 cases and 150 controls). Serum levels of calcium, creatinine, parathyroid hormone, and 24h urine metabolites were measured. Two polymorphisms, rs1801725 and rs1042636, of the CaSR gene, have been genotyped for each participant. T test, binary logistic regression, and Chi-square analysis were used for statistical analysis. Renal stone patients had significantly higher levels of serum parathyroid hormone, creatinine, and 24-h urine metabolites in comparison to the controls. CaSR gene variants, rs1801725 (GG) and rs1042636 (AA), both have shown significant association with renal stone disease. In addition, individuals having specific genotypes along with metabolic abnormalities such as hypercalcemia and hyperparathyroidism are found to be at a higher significant risk of developing the renal stone disease. In the present study, the haplotype of the CaSR gene has shown an association with renal stone disease. Individuals with hyperparathyroidism and hypercalcemia and risk genotype have a higher susceptibility to developing renal stone disease.

Some New Aspects of Genetic Variability in Patients with Cutaneous T-Cell Lymphoma.

Cutaneous T-cell lymphoma (CTCL) is a group of T-cell malignancies that develop in the skin. Though studied intensively, the etiology and pathogenesis of CTCL remain elusive. This study evaluated the survival of CTCL patients in the 1st Department of Dermatovenereology of St. Anne's University Hospital Brno. It included analysis of 19 polymorphic gene variants based on their expected involvement in CTCL severity. 75 patients with CTCL, evaluated and treated at the 1st Department of Dermatovenereology of St. Anne´s University Hospital Brno, Faculty of Medicine, Masaryk University, were recruited for the study over the last 28 years (44 men and 31 women, average age 58 years, range 20-82 years). All patients were genotyped for 19 chosen gene polymorphisms by the conventional PCR method with restriction analysis. A multivariate Cox regression model was calculated to reveal genetic polymorphisms and other risk factors for survival. The model identified MDR Ex21 2677 (rs2032582) as a significant genetic factor influencing the survival of the patients, with the T-allele playing a protective role. A multivariate stepwise Cox regression model confirmed the following as significant independent risk factors for overall survival: increased age at admission, clinical staging of the tumor, and male sex. We showed that the TT genotype at position 2677 of the MDR1 gene exhibited statistically significant longer survival in CTCL patients. As such, the TT genotype of MDR1 confers a significant advantage for the CTCL patients who respond to treatment.

The intestinal sutures insufficiency: factors of risk and prognostication, based on genetic investigations

Objective. To improve the results of treatment in patients, suffering insufficiency of sutures of intestinal anastomoses, using analysis of rate in the genes polymorphous variants of the matrix metalloproteinase Type 2 (C-1306 →T) and the tissue inhibitor of the matrix metalloproteinase Type 2 (G303 →A), as well as the result of elaboration of genetic diagnosis and prognostication of such complication.
 Materials and methods. In 32 patients, suffering insufficiency of intestinal sutures, which were treated in Shalimov National Institute of Surgery and Transplantology during 2016 - 2021 yrs, there were conducted the laboratory, genetic, immunohistochemical and statistical investigations.
 Results. Genetic and statistical analysis for the genes polymorphism of the matrix metalloproteinase Type 2 (C-1306 →T) and the tissue inhibitor of the matrix metalloproteinase Type 2 (G303 →A) have permitted to determine the genotypes variants, associated with risk for the sutures insufficiency occurrence in the hollow gut organs anastomoses. Basing on the data obtained, the prognostication method was elaborated for the sutures insufficiency occurrence in intestinal anastomoses. Such complications are occurred in 1,36 times more frequently in carriers of homozygous СС genotype in gene of the matrix metalloproteinase Type 2 and in two times lesser (5.9%) in carriers the minor homozygotes ТТ, than in the control - 10% (p>0.05). Among the patients with the sutures insufficiency of intestinal anastomoses a statistically significant in 1,6 times more frequent rate of carriers of the homozygous GG gene variant the tissue inhibitor of the matrix metalloproteinase Type 2 was revealed. Carriers of the minor homozygotes АА among the patients with the sutures insufficiency in intestinal anastomoses were absent, while the same genotype was revealed in the control with the 10% (p<0.05) rate. With objective to study the occurrence risk for the sutures insufficiency in intestinal anastomoses in presence of association in the studied genotypes we have analyzed several clinic-laboratory indices. There was revealed the pathogenetic significance of alleles of the genes polymorphic variants of the matrix metalloproteinase Type 2 and the tissue inhibitor of the matrix metalloproteinase Type 2, which were accompanied by hypoproteinemia, high indices of biochemical markers of collagen biodegradation and lowered expression of monoclonal antibodies for α-гладкоmuscular actin and collagen IV, and, finally. have evolved as the risk factors for development of the sutures insufficiency in intestinal anastomoses.
 Conclusion. The method proposed consists of genetic investigation of the genes polymorphism of the matrix metalloproteinase Type 2 (C-1306 →T) and of the tissue inhibitor of the matrix metalloproteinase Type 2 (G303 →A). It permits to prognosticate the probability of the sutures insufficiency development in intestinal anastomoses, and, basing on this, to improve the choice of the patients’ treatment tactic.

Some pharmacogenetic aspects of the <i>ABCB1</i> gene in lopinavir / ritonavir concentration variability in children with HIV infection: A pilot study

Polymorphic variants of the multidrug resistance gene (ABCB1 or MDR1) are associated with changes in the absorption and transport of drugs in the body. One of the substrates of the ABCB1 transporter is an antiretroviral drug from the class of protease inhibitors, lopinavir. The aim. To research the effect of polymorphic variants C1236T and C3435T in the ABCB1 gene on the plasma concentration of lopinavir / ritonavir in children and adolescents living with HIV infection. Methods. The genotypes of polymorphic variants of the ABCB1 gene were identified in 136 HIV infected children and adolescents; median age – 10 [7–12] years. The plasma concentration of lopinavir / ritonavir was measured from blood taken during the next scheduled appointment as part of dispensary observation at the Irkutsk Regional AIDS Centre using high performance liquid chromatography. Results. The average duration of lopinavir/ritonavir use as part of an antiretroviral therapy was 55 months. Median viral load in patients was 1 [1–2.03] log 10 copies/ mL; the number of CD4 + T cells – 38.36 %. The frequency of occurrence of the 3435T and 1236T alleles of the ABCB1 gene was ~50 %. In carriers of the 3435TT genotype, the median lopinavir concentrations 2 and 12 hours after drug intake were 5050.8 [3615.8–5847.7] and 2665.5 [216–4896.3] ng/mL, respectively. In carriers of the 1236TT genotype, median lopinavir concentrations 2 and 12 hours after drug intake were 4913.5 [3355.1–5733.7] and 3290.6 [159.1–4972.5] ng/mL, respectively. Conclusions. The study did not reveal a significant relationship between the carriage of the C3435T and C1236T genotypes of the ABCB1 gene and the concentrations of lopinavir and ritonavir 2 and 12 hours after drug intake.

The Role of Certain Polymorphic Variants in Genes, Previously Associated with Blood Pressure Values, with Reference to the Risk of Development of Coronary Artery Disease

Abstract The aim of the study was to analyze the effect of polymorphic variants previously associated with arterial hypertension (AH) in Genome Wide Association Studies (GWASs) in/next to genes and locuses CYP7A1 and PLEKHA7 on the development of coronary artery disease (CAD) in Bulgarian patients. A hundred and nine consecutive patients with angiographically documented CAD were studied. The genotyping was done with 7900 HT Fast Real-Time PCR (Applied Biosystems) with TaqMan® method. The control group consisted of 192 healthy population controls, selected from the bio- bank of the Molecular Medicine Center. SPSS and PLINK were used for the statistical analysis with level of significance < 0.05 and confidence interval 95%. The mean age of the studied patients was 63.71 ± 9.35 years; 35 (35%) females. Previous myocardial infarction (MI) had 38(38%); one-vessel – 39 (39%); two-vessel – 28 (28%); three-vessel disease – 34 (34%); 43 (43%) were with diabetes mellitus; 92 (92%) – with arterial hypertension (AH); 77 (77%) – with dyslipidemia; 42 (42%) were smokers; 25 (25%) were obese. We did not find any significant association between CAD and poly- morphism rs11191548 near CYP17A1 and only a tendency for genotype of rs381815 in PLEKHA7 (p = 0.06; OR 0.64; CI 0.40-1.02 for CAD) under dominant model. This is of practical importance both for studying the genetic aspects of CAD in the future and for enlargement of the current database.

IL1B gene variants, but not TNF, CXCL8, IL6 and IL10, modify the course of cystic fibrosis in Polish patients.

Background: The main aim of this study was to evaluate whether selected polymorphic variants in genes from the inflammatory pathway can be predictors of pulmonary or digestive manifestation of cystic fibrosis, as well as of severity of lung disease. Materials and methods: Using pyrosequencing and sequencing we have genotyped 12 variants in TNF (rs361525, rs1800629), CXCL8 (rs4073, rs2227306, rs2227307, rs188378669), IL1B (rs16944, rs1143634, rs1142639, rs1143627), IL6 (rs1800795) and IL10 (rs1800896) genes in a cohort of 55 Polish patients with diagnosed cystic fibrosis and controls. In our study group, a pulmonary manifestation of disease revealed 44 of subjects (80%), and digestive symptoms dominated in 11 (20%) of analyzed individuals. Severe lung dysfunction has occurred in 20 (36.4%) of patients. Results: We proved, that two promoter variants of IL1B, rs1143627 (c.-118G > A) and rs16944 (c.-598T > C) are presented significantly more often in patients with severe character of lung disease compared to mild (82.5% vs. 62.8%, p-value 0.030, and 87.5% vs. 64.3%, p-value 0.008, respectively) in cystic fibrosis course. Haplotype AC formed by both changes had also a higher frequency (80%) in patients with severe course compared to the mild character (61.4%) of disease. However, the frequency of promoter variant TNF c.-308C > T (rs1800629) was presented at a significantly lower level in the patient's group compared to healthy controls (2.7% vs. 15%, p-value 0.001). Furthermore, the presence of methicillin-resistant Staphylococcus aureus significantly correlated with the lower FEV1% in patients (p-value 0.01). Conclusions: Genetic variants, rs1143627 and rs16944, of IL1B are promising candidates as predictors of the severe character of lung disease in Polish patients with cystic fibrosis.

Склонность к риску и устойчивость к стрессу как факторы принадлежности к профессиональным и досуговым группам и их ассоциация с шестью генами-кандидатами

The search for sensations is a complex set of behavioral responses that are significant features of a person's personality. The purpose of this study was to identify differences in the occurrence of allelic variants of the OXTR, HTR2A, HTR2C, CRHR1, BDNF, AR genes in two groups of men practicing risky behavior (racers and paratroopers) compared with the control sample; identification of differences in the frequencies of polymorphic variants of candidate genes in riders and paratroopers. Materials and methods. The materials for this article were collected (buccal epithelium or saliva) in the period from 2017 to 2021 in the Moscow, Smolensk, Nizhny Novgorod regions and the city of Togliatti during the stages of the Russian Cup in auto racing (racers – 55 people), in the Republic of Kabardino- Balkaria at the mountaineering base "Bezengi" (paratroopers – 84 people), as well as the village of Bogovarovo, Kostroma Region (control sample: men and women – 214 people). Genotyping of the samples was carried out using PCR-RFLP and fragment analysis. With the help of population genetic analysis, the studied samples were characterized by a number of parameters (frequency of genotypes and alleles, expected heterozygosity). The similarity/difference of the samples in the genetic structure of the six genetic loci used was assessed using the G-test, Ney genetic distances and principal coordinates method, as well as analysis of molecular variability (FST) and Bayesian cluster analysis. Results. Some difference in the genetic structure of the sample of paratroopers from the control for all six loci, and racers from the control sample for the part of the loci used was shown. Discussion. The results obtained revealed the following: 1. persons practicing risky behavior are generally characterized by a certain genetic profile, in particular, according to the polymorphisms tested in our study; 2. individuals who demonstrate a willingness to take risks as part of their professional activities differ from those who prefer risky hobbies in terms of the combination of polymorphisms tested in our study, and are genetically predisposed to greater mental resistance to stress, conscientiousness and diligence, conscientiousness and extraversion.

Genetic predisposition to gestational diabetes mellitus in the Kazakh population

Background and aimsThe purpose of the study was to conduct a comparative analysis of population frequencies of alleles and genotypes of polymorphic variants of genes for impaired insulin synthesis and associated with insulin signal transduction. MethodsThis investigation uses a genomic database of 1800 conditionally healthy individuals of Kazakh ethnicity, who underwent full genome genotyping using OmniChip 2.5–8 Illumina chips of ∼2.5 million Single Nucleotide Polymorphism at deCODE Iceland Genomic Centre. ResultsThe highest frequency of carriage of minor A allele – 17.6% rs4607517 polymorphism of Glucokinase gene, unfavorable genotypes A/G – 29.5% and A/A – 3.0% in comparison with European and Asian populations, indicates a contribution of hereditary family forms of Maturity-onset diabetes of the young type 2 to gestational diabetes mellitus in Kazakh population. ConclusionsThe study of the associations of genetic markers of gestational diabetes mellitus will allow timely identification of high-risk groups before and at an early stage of pregnancy, carrying out the necessary effective preventive measures and, in the case of gestational diabetes mellitus development, optimizing the correction of carbohydrate metabolism disorders and predicting outcomes for the mother and the fetus.

VEGF gene polymorphism in complicated infective endocarditis

Introduction. Infective endocarditis (IE) is a bacterial disease with frequent pathogen localization on the heart valve apparatus. IE is characterized by rapid development of heart failure and frequent thromboembolic complications (TEC). IE features are accounted for by foreign pathogen nature and state of human immune system (IS). The imbalanced IS in infective endocarditis is manifested by impaired cytokine-mediated interactions. This confirms the rationality of studying cytokines to advance understanding of the pathogenesis for various conditions. Most cytokine genes are characterized by polymorphism and existing isoforms underlying disease predisposition. Genetic polymorphism of vascular endothelial growth factor A (VEGF-A) plays an important role in the induction of vasculogenesis and angiogenesis. The pathogenetic VEGF role in IE has not been thoroughly studied. Research objective analysis of polymorphic nucleotide sequence variants in the vascular endothelial growth factor gene, taking into account a relation with its serum concentration in patients with infective endocarditis. Materials and methods. 86 patients treated with verified diagnosis of infective endocarditis at the Scientific Research Institute Regional Clinical Hospital No. 1 of Krasnodar were divided into two clinical groups in accordance with the IE course: Group 1 IE with TEC (n = 44), group 2 IE without TEC (n = 42), and the control group consisted of 20 apparently healthy individuals. The concentration of serum VEGF-A (pg/mL) was measured by ELISA on day 1 of hospitalization. Genomic DNA was isolated from whole blood leukocytes and used to determine the frequency of genotypes of VEGF gene polymorphic variants. Results. Significant differences in the frequency distribution of VEGF-rs2010963 genotypes between patients with infective endocarditis and control group were revealed: G/G (OR = 0.25; p = 0.012) and G/C (OR = 4.28; p = 0.022), as well as differences between VEGF concentrations for various SNP-rs2010963 genotypes (p = 0.0001). A study of VEGF genotype frequency distribution between patients of clinical groups showed a significantly decreased frequency of the genotype G/G (rs2010963) in the IE group with TEC (OR = 0.21; p = 0.014) and increased frequency of G/C (OR = 4.72; p = 0.024) compared with the control group, whereas in patients with IE without TEC, significant (p = 0.0003) differences in serum concentrations of VEGF-rs2010963 were found in accordance with genotypes GG/CC (p = 0.01) and GG/GC (p = 0.003). Conclusion. The relationship between the VEGF genotypes (G/G and G/C of rs2010963 polymorphism) and related serum concentration among patients with IE was revealed. Carriers of the minor C allele (rs2010963) had higher serum VEGF levels. The results obtained complement and systematize current scientific data on the disease pathogenesis, as well as focus on the genetic determinant of the developing complications.

Association of polymorphic variants in GEMIN genes with the risk of depression in a Polish population.

The role of miRNA in depression is widely described by many researchers. miRNA is a final product of many genes involved in its formation (maturation). One of the final steps in the formation of miRNAs is the formation of the RISC complex, called the RNA-induced silencing complex, which includes, among others, GEMIN proteins. Single-nucleotide polymorphisms (SNPs) may lead to disturbance of miRNA biogenesis and function. The objective of our research was to assess the relationship between the appearance of depression and single nucleotide polymorphisms in the GEMIN3 (rs197388) and GEMIN4 (rs7813; rs3744741) genes. Our research provides new knowledge on the genetic factors that influence the risk of depression. They can be used as an element of diagnostics helpful in identifying people at increased risk, as well as indicating people not at risk of depression. A total of 218 participants were examined, including individuals with depressive disorders (n=102; study group) and healthy people (n=116, control group). All the patients in the study group and the people in the control group were non-related native Caucasian Poles from central Poland. Blood was collected from study and control groups in order to assess the SNPs of GEMIN genes. An analysis of the results obtained showed that in patient population, the risk of depression is almost doubled by polymorphic variants of the genes: rs197388/GEMIN3 genotype A/A in the recessive model and rs3744741/GEMIN4 genotype T/T, codominant and recessive model. The dual role of rs7813/GEMIN4 is noteworthy, where the G/A genotype in the codominant and over dominant model protects against depression.

ASSOCIATION BETWEEN THE COMPLEX OF POLYMORPHIC
 VARIANTS OF DGAT1, GH, PRL AND BLG GENES AND MILK YIELD
 INDICATORS OF THE COWS OF THE BELARUSIAN RED BREED
 GROUP

When assessing an associated effect of the complex of polymorphic variants of genes of diacylglycerol O-acyltransferase 1 (DGAT1), somatotropin (GH), prolactin (PRL), beta-lactoglobulin (BLG) with the dairy productivity indicators of cows of the Belarusian red breed group, it was found that the highest indicators were demonstrated by the animals with the complex genotype DGAT1KK GHLL PRLAA BLGAB.

Investigation of allele frequencies of polymorphic variants in genes that are related to polycystic ovary syndrome.

Polycystic ovary syndrome is a hormonal disorder that normally affects women of reproductive age in the range of 18-44 years. This study aimed to investigate the allelic frequencies of two polymorphisms, IRS rs18012781 and INSR rs1799817, which are suspected to be involved in polycystic ovary syndrome. The samples were obtained from the patients admitted to the Near East University Hospital, Department of Gynecology and Obstetrics. The samples were divided into two groups: control and polycystic ovary syndrome groups. Blood samples were collected from 55 women in the control group and 65 samples from the patient group. DNA from whole blood was obtained. The allelic frequencies of single-nucleotide polymorphisms were determined using real-time PCR. Results were presented as the heterozygous and homozygous state of the single-nucleotide polymorphisms. There were no significant differences in the allelic frequencies of the single-nucleotide polymorphisms between the patient and control groups. Further statistical analysis investigating the INSR Tm using the Mann-Whitney U test value revealed that there was no difference in the homozygous and heterozygous state of INSR rs1799817. The result of this study showed that there was no statistically significant difference between the allelic frequencies of IRS1 rs1801278 and INSR rs1799817 between the patient and control groups. These single-nucleotide polymorphisms do not seem to modify the risk of polycystic ovary syndrome, and they cannot be used as a marker in clinical circumstances to evaluate the possible occurrence of polycystic ovary syndrome.

The Roles of MTRR and MTHFR Gene Polymorphisms in Colorectal Cancer Survival.

Paradoxically epidemiological data illustrate a negative relationship between dietary folate intake and colorectal cancer (CRC) risk. The occurrence and progression of CRC may be influenced by variants in some key enzyme coding genes in the folate metabolic pathway. We investigated the correlation between genetic variants in methionine synthase reductase (MTRR) and methylenetetrahydrofolate reductase (MTHFR) and CRC survival. This study used data collected from the Newfoundland Familial Colorectal Cancer Study. A total of 532 patients diagnosed with CRC for the first time from 1999 to 2003 were enrolled, and their mortality were tracked until April 2010. DNA samples were genotyped by Illumina's integrated quantum 1 million chip. Cox models were established to assess 33 tag single-nucleotide polymorphisms in MTRR and MTHFR in relation to overall survival (OS), disease-free survival (DFS) and CRC-specific survival. The MTRR and MTHFR genes were associated with DFS and CRC-specific survival in CRC patients at the gene level. After multiple comparison adjustment, MTRR rs1801394 A (vs. G) allele was associated with increased DFS (p = 0.024), while MTHRT rs3737966 (G vs. A), rs4846049 (T vs. G), rs1476413 (A vs. G), rs1801131 (C vs. A), rs12121543 (A vs. C), rs1801133 (C vs. T), rs4846052 (T vs. C), rs2066471 (A vs. G) and rs7533315 (T vs. C) were related to worse CRC-specific survival. Additionally, significant interactions were seen among pre-diagnostic alcohol consumption with MTRR rs1801394, rs3776467, rs326124, rs162040, and rs3776455, with superior OS associated with those protective variant alleles limited to patients with alcohol consumption under the median. The MTHFR rs3737966 (G vs. A) allele seemed to be detrimental to CRC survival only among subjects with fruit intake below the median. Polymorphic variants in MTRR and MTHFR genes that code for key enzymes for folate metabolism may be associated with survival in patients with CRC. The gene-CRC outcome association seems modulated by alcohol drinking and fruit intake.

Human Induced Pluripotent Stem Cell Phenotyping and Preclinical Modeling of Familial Parkinson's Disease.

Parkinson's disease (PD) is primarily idiopathic and a highly heterogenous neurodegenerative disease with patients experiencing a wide array of motor and non-motor symptoms. A major challenge for understanding susceptibility to PD is to determine the genetic and environmental factors that influence the mechanisms underlying the variations in disease-associated traits. The pathological hallmark of PD is the degeneration of dopaminergic neurons in the substantia nigra pars compacta region of the brain and post-mortem Lewy pathology, which leads to the loss of projecting axons innervating the striatum and to impaired motor and cognitive functions. While the cause of PD is still largely unknown, genome-wide association studies provide evidence that numerous polymorphic variants in various genes contribute to sporadic PD, and 10 to 15% of all cases are linked to some form of hereditary mutations, either autosomal dominant or recessive. Among the most common mutations observed in PD patients are in the genes LRRK2, SNCA, GBA1, PINK1, PRKN, and PARK7/DJ-1. In this review, we cover these PD-related mutations, the use of induced pluripotent stem cells as a disease in a dish model, and genetic animal models to better understand the diversity in the pathogenesis and long-term outcomes seen in PD patients.

Modern Aspects of Anticoagulation System Disorders Diagnosis in Children with Different Polymorphisms in Coagulation Genes. Initial Results

Background. Hemostatic system pathology is topical and poorly studied issue in pediatrics. One of the main causes of coagulation pathway disorders associated with thrombotic events is abnormality in various parts of the hemostatic system. Vascular accidents are commonly caused by anticoagulation system factors deficiency. Conventionally, thrombosis is a common event in adult patients, and there is no adequate attention to disorders of primary physiological anticoagulants system in children. More often acquired anticoagulant proteins deficiency develops in presence of various pathological conditions, especially after the past infectious diseases. All these diseases (thrombophilia, trombotic events, cardiovascular pathology, nervous system diseases, genetic diseases) can occur separately and in association with each other, plus clinical picture of coagulation events may be similar. Objective. The aim of the study is to evaluate changes in the physiological anticoagulants system in children with different pathologies who have polymorphic variants in coagulation genes and who had new coronavirus infection. Methods. The study included 33 children who had severe coronavirus infection in family clusters and had severe chronic pathology potentially associated with disorders of the coagulation system (nervous system damage, hypertrophic cardiomyopathy, hereditary monogenic syndromes, hemato-mesenchymal dysplasia syndrome). All children underwent complete examination including clinical examination, laboratory, and instrumental diagnostics. Results. Preliminary study results indicate significant incidence of polymorphic variants in coagulation genes (one third of children with various diseases from the study). Some children had decreased activity of anticoagulation system glycoproteins (from 6% to 36%) that confirmed the topicality of the examination of anticoagulation system factors deficiency and the need for further dynamic follow-up, as well as revealing of trombophilia predictors in children in selected target groups. Study on revealing anticoagulation system disorders and mutations in coagulation genes will predict the risk of thrombotic disorders. Conclusion. The obtained results have confirmed the significant role of the ongoing study for comprehensive assessment of hemostatic system disorders in children. That will allow us to optimize the approach to diagnosis and personalize the management strategy for patients with different chronic pathologies and disorders of the natural anticoagulants system. The study is currently ongoing.

ПОЛИМОРФИЗМ BSMI ГЕНА РЕЦЕПТОРА ВИТАМИНА D И ЭФФЕКТИВНОСТЬ ЛЕЧЕНИЯ ПОСТМЕНОПАУЗАЛЬНОГО ОСТЕОПОРОЗА ИБАНДРОНОВОЙ КИСЛОТОЙ

An assessment of genetic factors influence on ibandronic acid effect in postmenopausal osteoporosis treatment can significantly bring us closer to the practical use of this results in prognostic genetics and personalized medicine. The aim was the study of associations between 283 A>G (BsmI, rs1544410) polymorphisms of vitamin D receptor gene (VDR) and ibandronic acid efficacy in postmenopausal osteoporosis treatment.
 117 women with postmenopausal osteoporosis were examined through treatment dynamics. A 12-month therapy course included the use of ibandronic acid according to standard regimen. Evaluation of treatment effectiveness was carried out by changes (%) in bone mineral density (BMD) separately for each area by dual- energy X-ray absorptiometry. Real-time PCR was used to determine VDR gene rs1544410 polymorphism.
 It was found that for 12 months ibandronate use caused significant (p<0.001) BMD increase. BMD increase ranged from 2.71±0.53% in left femoral neck zone to 4.63±0.53% in the L1-L4 lumbar vertebrae. The treatment outcome did not depend (p>0.05) on age, height, weight, body mass index, and postmenopause duration. GG genotype of rs1544410 polymorphism was associated with lower BMD growth rate in L1-L4 lumbar vertebrae (p=0.036).
 Screening of women with postmenopausal osteoporosis for polymorphic variants of VDR gene (rs1544410) before antiresorptive therapy with ibandronic acid may be appropriate to predict the effect and individualize treatment and prophylactic measures. The obtained results can contribute to more complete understanding of osteoporosis pharmacogenetics