Autosomal recessive polycystic kidney disease (ARPKD, Polycystic kidney disease 4 with or without hepatic disease, MIM 263200) is a severe genetic disorder with variable clinical spectrum. It is an important cause of renal-related and liver-related morbidity and mortality. ARPKD is caused by mutations in the PKHD1 gene which was mapped to chromosome 6p21-p12. A 67-exon transcript encodes one of the lon- gest continuous open reading frame. Protein polyductin is synthesized from this transcript. Mutations were found to be scattered through- out the gene without evidence of clustering. Searching for mutations is time-consuming and costly. We identified new variant c.9071G>A (р.Cys3024Tyr) in 14 families on 16 chromosomes which makes 12.7% mutations. This variant did not found on 1008 control chromosomes. Mutation c.107C>T (р.Thr36Met) occurs in 53% families with mutation on 41% chromosomes. Mutations c.1486C>T (р.Arg496Ter) and c.9524A>G (р.Asn3175Ser) occur in 10% families each. Mutation analysis in PKHD1 gene is very important for confirming the ARPKD diag- nosis and genetic counseling with following prenatal diagnosis.

Wilson-Konovalov’s disease (WD) is a rare inborn disease characterized by excess accumulation of copper in parenchymal tissues. WD is caused by pathogenic variants in the ATP7B gene, such as missense variants, insertion/deletion. The results of study of allelic frequencies of insertion/deletion in ATP7B gene in Russian WD-patients are presented in this research. The mutations: c.1770insT, c.2304insC, c.2532delA, c.3036insC, c.3402delC, c.3627_3642del4, c.3649_3654del6, c.[3942delCA;3947delG] were included to the screening system for frequent ins/ del in ATP7B gene.

Introduction: Implementation of the clinical decision support systems capable of forming the recommendations on drug and dose selec- tion according to the results of pharmacogenetic testing is an urgent task. Fulfillment of this task will allow increasing the efficacy of ther- apy and decreasing the risk of undesirable side effects.Materials and methods: The study involved 51 patients (21 - the main group receiving appointments in accordance with the recommenda- tions based on the results of pharamogenetic testing, and 30 - the comparison control group receiving appointments without them) male with alcohol withdrawal syndrome. In order to assess the effectiveness and safety of alcohol withdrawal syndrome, which was performed with the benzodiazepine tranquilizer of phenazepam (bromodihydrochlorophenylbenzodiazepine), as well as standard detoxification and vitamin therapy, international psychometric scales and scales of assessment in expressions of adverse reactions. Genotyping Determination of genetic polymorphisms CYP2D6*4 (1846G>A, rs3892097), CYP2C19*2 (681G>A, rs4244285), CYP2C19*3 (636G>A, rs4986893), CYP2C19*17 (-806C>T, rs12248560), CYP3A5*3 (6986A>G, rs776746) and ABCB1*6 (3435C>T, rs1045642) were realized using real-time polymerase chain reaction with allele specific hybridization. Interpretation of the results of pharmacogenetic testing was carried out with the help of free soft- ware PharmacoGenomeX2 (www.pgx2.com)Results: Statistically significant differences in the number of scores for all psychometric scales in the patients of the main group and the comparison group were obtained. For example, on the scale of assessing the severity of alcohol withdrawal syndrome by the 3rd day of the study, the score in the main group was 13.5 [11.2; 16,0], and in the control group - 18,0 [17,0; 22.0] (p <0.001); to the 5th in the main group - 6.5 [4.2; 8.0], in the control group - 15.0 [14.0; 16.0] (p <0.001). On the UKU security scale, a statistically significant difference was also obtained. By the 3rd day of the study, the UKU score in the main group was 6.0 [5.0; 7,0], and in the control group - 7,0 [6,0; 8.0] (p = 0.030); by the 5th day the difference increased. In the main group, 5.5 [3.0; 9.0], in the control group - 14.0 [12.0; 19.0] (p <0.001). The groups were representative (when included in the study, the difference in the number of points was absent).Conclusion: Personalization of the dose of drugs in accordance with pharmacogenetic algorithms in patients with alcohol withdrawal syn- drome, can reduce the risk of unwanted reactions and pharmacoresistance, which allows to recommend the use of pharmacogenetic deci- sion support systems for drug dosage selection.

Background. Adiponectin (AN) - a protective adipocytokine, produced by fat tissue and circulating in the form of various isomers in the blood. With obesity, a decreased level of AN is associated with the development of metabolic syndrome (MS) and various cardiovascular diseases. Regulation of its level can be caused by genetic factors, including single nucleotide polymorphism T(+45)G and C(-11377)G of the ADIPOQ gene. Allelic variants of the ADIPOQ gene was associated with AN concentrarion in blood.Objective. To identify the association of genetic variants of ADIPOQ with adiponectin level, AO and MS in women.Results. A total of 302 women with abdominal obesity (AO) aged 30-55 years were examined. The comparison group consisted of 161 practically healthy women without AO. 185 patients with AO had MS according to the criteria of the International Diabetes Federation (IDF, 2005). The frequencies of genotypes and alleles of variants T (+45) G and C (-11377) G of the ADIPOQ gene among women with and without AO did not differ (p> 0,05). Among women with AO and MS, carriers of G allele variant T (+45) G of the ADIPOQ gene were less common than among women with AO without MS (р<0,05). The frequencies of genotypes and alleles of variant C (-11377) G of the ADIPOQ gene did not differ in women with AO and MS and in patients with AO without MS (p> 0.05). In women with AO - carriers of the G allele variant T (+45) G of the ADIPOQ gene, the concentration of high molecular weight AN (HMWA) was higher than that of the TT carriers of the genotype of this gene The haplotypes of the T (+45) G and C (-11377) G variants of the ADIPOQ gene did not differ in the studied groups (p> 0,05). The con- centration of total AN in the serum of women with AO and MS - carriers of different genotypes and haplotypes of variants T (+45) G and C (-11377) G of the ADIPOQ gene did not differ (p> 0,05). The concentration of HMWA in women with AO - carriers of the TGC(X) haplotype (X - allele C or G variant C (-11377) G) was higher than in women with AO - carriers of other haplotypes of the ADIPOQ gene (p <0,05). Coclusions. G allele of the T(+45)G variant the ADIPOQ gene is protective against MS in women with AO. In women with AO - carriers of the G allele, the concentration of HMWA is higher than in women with AO - carriers of the TT genotype of variant T(+45)G of the ADIPOQ gene.

Preeclampsia (PE) is one of the most serious hypertensive pregnancy disorders, which etiology and pathogenesis is remained poorly under- stood. Since a key role in the etiopathogenesis of PE is given to the placental tissue, the study of the gene expression variability in the pla- cental tissue and of the regulatory mechanisms of these changes is a promising approach. The purpose of this research was to characterize of the genetic architecture of PE on the basis of regulatory polymorphic variants (rSNPs) of the new SYDE1 candidate gene, identified for the first time by the results of the transcriptome analysis in placental tissue. In this work, we analyzed the two most significant rSNPs of the SYDE1 gene (rs56153523, rs8109071). The study was conducted in three ethnic groups: Buryats, Russians, Yakuts. We have detected associations of the rSNPs of SYDE1 gene with the development of preeclampsia in ethnic groups Buryat (rs56153523) and Russian (rs56153523, rs8109071).

Introduсtion: Hypertensive disorders complicate a significant number of pregnancies and, thereby, increase the number of maternal and neonatal mortality, as well as the incidence of morbidity. The study of genes that may affect the risk of developing this complication of gestation contributes to a complete understanding of the pathogenesis and the definition of the therapeutic goals of this disorder.IISSSSNN 22007733--77999988 39Objective: analysis of the association of gene CYP11B2 polymorphism -344C> T with the risk of hypertensive disorders during pregnancy among Uzbek women.Study design: the study included a group of 201 pregnant women with hypertensive disorders, who made up the main group, divided into 3 subgroups: subgroup A - 41 pregnant women with chronic arterial hypertension (CAG), subgroup B - 110 pregnant women with gesta- tional hypertension (GH), subgroup B - 50 pregnant women preeclampsia (PE). The control group consisted of 110 healthy women of repro- ductive age without chronic diseases and severe obstetric pathology in history. All women were Uzbek nationality. Determination of poly- morphism -344C> T CYP11B2 gene was performed by PCR on an Applied Biosystems 2720 device (USA), using the set of Liteh LLC (Moscow). Results: According to the results of our studies in pregnant women of Uzbek nationality, with hypertensive disorders, a high carrier fre- quency was found for the functionally unfavorable T allele and the homo / heterozygous C / T and T / T genotypes of the -344C> T CYP11B2 polymorphism compared with the control sample. The level of statistical significance of differences in the frequency of the T allele and the C / T and T / T genotypes between the studied groups of patients and the control sample was quite high. Accordingly, in T-allele carriers, C/ T and T / T genotypes, the risk of developing hypertensive disorders was increased by 2.8, 1.7, and 7.3 times with χ2> 3.9; р <0.05. At the same time, the homozygous C / C genotype proved to be protective against the formation of hypertensive disorders in women. With this genotype, the risk of hypertensive disorders was reduced by more than 3 times (χ2 = 20.8; р <0.05; OR = 0.3; 95% CI 0.20-0.5). Results of our studies encourage for further searches of genetic polymorphisms, to predict the risk of developing hypertension in women of Uzbek eth- nicity and to develop appropriate preventive measures.

This article presented below reflects modern ideas about the combination of several hereditary syndromes as a result of an contiguous deletion of the X chromosome by the example of mucopolysaccharidosis type II and mental retardation. Monogenic syndromes occurring in the literature in combination, marked as contiguous gene syndromes, have been analyzed, along with what the notion of contiguous geneshas been described. Contiguous gene syndromes due to the deletion of the X chromosome region in boys lead to structural and functional nullisomy, thus confirming the significance of studying the number of copies of genes in order to determine the exact genetic defect. The data of the literature and our own observations concerning issues of etiology, pathogenesis, time of manifestation and clinical symptoms of the disease, diagnostic methods, treatment and prevention of mucopolysaccharidosis type II are summarized. Mucopolysaccharidosis type II refers to а group of lysosomal storage diseases with multiorgan lesions. Here is described a clinical case of Hunter syndrome with a long deletion of the X chromosome and an early manifestation of a combined stenosis of the spinal canal, the development of myelopathy of the cervical spinal cord as a result of the accumulation of glycosaminoglycans in the membranes of the spinal cord. The described case with the clinical picture of mixed tetraparesis is a rarer symptom with type II mucopolysaccharidosis than with other mucopolysaccharidosis and, as a rule, manifests at an older age. It was suggested that such a phenotypic correlation in patients with mucopolysaccharidosis type II, as a severe phenotype with neurological symptoms with a complete deletion of the IDS gene. The algorithm for examining patients with non-syndromic mental retardation includes the analysis of karyotype, DNA-diagnosis of fragile X chromosome, and chromosome analysis. It is shown that a survey is needed to exclude MPS II in boys with mental retardation and the inclusion of simple biochemical tests in these algorithms - determination of GAG in urine and analysis of lysosomal enzymes, which will more effectively identify patients with MPS type II.