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Background. Within the framework of the regional pilot project on selective exome screening of newborn children, which is carried out on the basis of the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, we conducted molecular genetic testing of children who meet the criteria for inclusion in the increased group of hereditary diseases. We examine not only children with suspected genetic etiology of the condition, but also children with borderline clinical and laboratory manifestations and minor developmental anomalies.The aim of the study. To describe the clinical and phenotypic features of a patient with a previously undescribed Xq12q13.2 duplication detected in the neonatal period.Materials and methods. The child was examined within the framework of a regional pilot project on selective exome screening of newborn children. DNA was isolated from a biological sample of venous blood of the newborn, and whole exome sequencing and chromosomal microarray analysis were performed. Signed informed voluntary consent for the publication of the examination data and a photograph of the child were obtained from the legal representatives of the proband.Results. Data in favor of the presence of a previously undescribed Xq12q13.2 duplication, confirmed by the reference method were obtained in a patient included in the project in accordance with the clinical criteria for the formation of a risk group according to the data of the conducted whole exome sequencing. Discussion. Xq12q13.2 duplication was detected in the proband from the present clinical observation with non-specific clinical manifestations in the neonatal period. Similar duplications have been described in the literature in three patients with congenital malformations, epilepsy and psychomotor retardation. Early diagnosis of such a copy number variation disorder before the appearance of severe clinical signs of the disease will allow determining the prognosis and tactics of observation and treatment of the patient.Conclusion. The described case of Xq12q13.2 duplication in a patient demonstrates the importance of timely genetic analysis to optimize medical genetic counseling, reduce diagnostic search and improve prognosis for patients.

Background. Core biopsy of the breast is currently considered to be the standard method of obtaining material for morphological and molecular genetic methods. Unfortunately, this method is associated with a number of problems, primarily the risk of complications (bleeding, pneumothorax) and discomfort during manipulation.Aim. To analyze transcriptional signatures of breast tissue samples obtained by fine-needle aspiration biopsy. Materials and methods. Using reverse transcriptase polymerase chain reaction, we studied the mRNA expression level of 60 target genes in 60 samples obtained by fine-needle aspiration biopsy and in 60 corresponding formalin-fixed paraffin-embedded (FFPE) surgical specimens of breast. Samples were obtained from the tumor, adjacent tissue, the so-called tumor bed and formally normal tissue at a distance from the primary lesion.Results. A comparative analysis of transcriptional signatures in samples obtained by fine-needle aspiration biopsy and FFPE specimens (120 samples in total) reveled the strongest correlations between transcriptional signatures in biopsy samples and FFPE specimens of tumors. Very strong correlation in tumor samples was established for one gene (CTSL2); strong for 18 genes (MKI67, MYBL2, NAT1, PTEN, TPX2, PTTG1, UBE2T, CCNB1, ESR1, CCND1, MYC, SCGB2A2, MIA, TRAC, FGFR4, ANLN, GSTM1, PRLR); averages for 28 genes (PGR, AURCA, KRT5, FOXA1, SFRP1, EMSY, EXO1, PAK1, KIF14, ERBB2, MMP11, BCL2, BAG1, TMEM45B, BIRC5, CD274/PDL1, ZNF703, TYMS, CCNE1, TPT1, TMEM45A, BRCA1, BRCA2, ESR2, STS, TNFSF11/RANKL, TNFRSF11B/OPG, TNF); weak for 4 genes (GRB7, EGFR, PGRMC1, CYP19A). The presence of correlations between transcriptional signatures in biopsy samples and FFPE specimens can be established in case of sufficient material corresponding to sample intake control (SIC) ≥5 lg for B2M gene.Conclusion. The ability to conduct molecular genetic research on small samples of breast tissue makes it possible to obtain the material using the most minimally invasive method. And this, in turn, expands the possibilities of “genetic monitoring” of cancer, as well as the possibility of more accurate assessment the risks of malignant tumor development in the settings of benign conditions in women with fibrocystic disease and increased mammographic density.

Background. Atypical ductal hyperplasia is a relatively common breast lesion that increases the risk of breast cancer by 3.5 to 5 times. Genomic rearrangements underlying the development of atypical proliferative lesions and breast cancer lead to gene expression changings.Aim. To determine the mRNA expression profile of neoplasia and oncogenesis driver genes in atypical ductal hyperplasia of the breast.Materials and methods. The real-time reverse transcription polymerase chain reaction was used to explore the expression profile of 46 genes in 107 samples of formalin-fixed paraffin-embedded (FFPE) specimens from atypical ductal hyperplasia, ductal hyperplasia without atypia, ductal carcinoma in situ and normal breast tissue.Results. In atypical ductal hyperplasia, we detected changes in the expression of 22 of 46 studied genes, including ESR1, AR, PRLR, FGFR4, MKI67, CCNB1, KIF14, PAK1, MMP11, GATA3, FOXA1, ZNF703, which were upregulated, and MYC, which was downregulated.Conclusion. The transcriptional signature of atypical ductal hyperplasia was similar to that of ductal carcinoma in situ and breast cancer of luminal subtypes.

Relevance. Acute respiratory infections (ARI) are a serious health problem not only because of the high frequency of their occurrence, but also because of the economic damage they cause both in the form of direct costs (the cost of diagnosis and treatment) and indirect costs (disability, reduced labor productivity, etc.). Pregnant women and children under 5 years of age are included in the group of patients with risk factors for complications of influenza and other ARI, therefore, an analysis of the etiological structure of ARI and influenza in obstetric hospitals is an urgent task. In recent years, there has been an urgent need to create a national complex diagnostic test system based on molecular genetic methods for detecting infectious agents that cause ARI. Aims. The aim of the study is to analyze the etiological structure of ARI and influenza in patients with clinical symptoms and to develop and implement a new test system for rapid screening and diagnosis of infections that cause ARI. Materials & methods. When studying the etiological structure of ARI and influenza, cultural studies of the nasal and pharyngeal mucosa were carried out, followed by identification of microorganisms using MALDI-TOF mass spectrometry and molecular genetic study (real-time PCR) using an experimental test panel containing primers that allow detecting the following viruses: influenza A, B viruses, parainfluenza viruses of the 1st, 2nd, 3rd and 4th types, coronaviruses OS43, HKU1, NL63, E229, respiratory syncytial virus, metapneumovirus, rhinovirus and adenovirus, as well as bacterial pathogens of ARI: Haemophilus influenzae, Streptococcus pneumoniae, Streptococcus pyogenes, Moraxella catarrhalis, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa. The test system was developed using the following methods: real-time PCR, a combination of reverse transcription and real-time PCR (RT-PCR) and the next generation sequencing (NGS) method. Results. The etiological structure of ARI and influenza was analyzed in patients with clinical manifestations (cough, tickling/sore throat/hyperemia of the mucous membrane of the palate and the back wall of the pharynx, shortness of breath/difficulty breathing, acute runny nose/nasal congestion). The species spectrum of bacterial and viral pathogens was revealed. A new test system based on PCR, real-time RT-PCR and NGS has been created for complex diagnostics of both viral and bacterial pathogens of ARI, consisting of three separate components: the main test system «ARI», which detects the main viral and bacterial pathogens of ARI, and two additional sets of reagents: «Oseltamivir resistance» and «Oseltamivir/ Zanamivir resistance». Conclusions. The new test system can be used to detect and differentiate nucleic acids of pathogens of ARI of humans. The test system seems to us promising for further use. As a result of the analysis of the etiological structure of acute respiratory infections and influenza, attention is drawn to a significantly smaller variety of identified pathogens in 2020 and a much more pronounced dominance of rhinovirus infection compared to our previous study in 2019.

Objective: to identify molecular genetic predictors of metastatic spread to regional lymph nodes in patients with breast cancer (BC) based on the analysis of gene expression profile of the primary tumor.Materials and methods. The study included 358 patients with BC who underwent surgical treatment in breast cancer department of Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia. Among all included into the study patients, 132 (36.9 %) had metastases in at least one axillary lymph node. Molecular genetic examination of the tumor tissue was carried out using reverse transcription polymerase chain reaction; the diagnostic panel consisted of 45 functional and 3 reference genes. Results. Patients with metastases to regional lymph nodes were generally younger (p = 0.006), had larger primary tumor (p

HPV infects epithelial tissues regardless of their location and penetrates into the cell through microscopic cuts. The clinical manifestations of HPV-associated diseases are diverse and equally relevant for women and men. Despite the fact that exophytic condylomas are regarded as a benign disease and establishing diagnosis does not cause difficulties, a clinician should always have oncological alertness, especially with regard to diffuse, long-lasting condylomatosis.

Relevance. Life expectancy of cystic fibrosis patients mostly depends on the degree of respiratory system damage caused by opportunistic microorganisms, which is due to the fact that 90-95% of deaths of cystic fibrosis patients are caused by lung infections. Goal. To define epidemiologic characteristics of chronic lung infection caused by the most common agents (S. aureus, P. aeruginosa, B. cepacia-like bacteria (Bcc) and Achromobacter spp.) using a novel chronic lung infection in cystic fibrosis patients microbiological diagnosis algorithm. Materials and methods. Over a period of 7 years (2008-2016) 300 children with cystic fibrosis living in Moscow, Moscow region and several other regions of Russian Federation have been checked-up. 260 sputum samples from 100 adult patients, who were under care at the Pulmonology Research Institute, were studied. Sputum samples from children were taken before and after antibiotic therapy with intervals of 15-45 days and over 6 months. 30 of the children were also subjected to a microbiologic monitoring of the state of chronic infection in the period between 4 and 15 months. Sputum sample from adult patients were also taken before and after antibiotic therapy with intervals of 0, 15-45 days and over 6 months. Results. P. aeruginosa, S. aureus, H. influenzae and Burkholderia cepacia-like bacteria were confirmed to be the most common agents of lung infection in cystic fibrosis patients. Children with cystic fibrosis over the years develop foci of chronic lung infection, mainly caused by P. aeruginosa and S. aureus. Conclusions. Chronic lung infection can be caused by community-acquired or nosocomial S. aureus и P. aeruginosa. Chronic lung infection is a complex, dynamically changing disease which requires constant monitoring and is mainly caused by S. aureus, P. aeruginosa, Bcc bacteria and Achromobacter spp. As populations of the agents can be diverse, it is necessary to study all colonies with differing phenotypes (mucoid and non-mucoid variants, small colony variants, variants with different pigments) and to take samples of several colonies when testing antibiotic resistance. Bcc and Achromobacter spp. cannot be eradicated with antibiotics, thus the only effective measure against these bacteria can only be vaccination which requires developing a vaccine.

More than 50% of pregnant women after the programs of assisted reproductive technologies (ART) face the problem of recurrent miscarriage (RMC), especially in the first trimester. Significant role in the development of RMC has infectious factor and chronic inflammation in the endometrium. The aim: to reveal the peculiarities of immune response mRNA genes of the inflammatory component expression in the period of the tentative implantation window (TIW) in women with RMC in ART programs. Material and methods. The main group consisted of 240 patients with RMC in ART programs; the control group included 100 conditionally healthy fertile women. On the ground of PCR reverse transcription, the mRNA of the IL-1β, IL-2, IL-10, Foxp3, TLR9, IL-2Rα cytokine genes was examined in endometrial samples obtained with the help of biopsy on the TIW day. Results. Analysis of the transcriptional profile of the immune response genes in the endometrium on TIW day revealed that the relative level of mRNA expression of the IL-1β, IL-2, Foxp3, TLR9, IL-2Rα genes did not differ significantly in the main and control groups. Statistically significant decrease in mRNA expression of IL-10 gene was observed in women with RPL. Conclusions. A feature of mRNA expression of the inflammatory component of the immune response in TIW period in women with RMC in ART programs is a decrease in the expression level of the IL-10 gene mRNA, which may be one of the reasons for the unfavorable outcomes of the onset pregnancy.

Objective: to investigate the distribution of the genotypes and alleles of the PTPN22, TNFAIP3, CTLA4, TNFA, IL6, IL6R, IL10, MCP1, and ICAM1 genes in patients with rheumatoid arthritis (RA) and in the control group of healthy individuals, to estimate their significance as molecular genetic markers for predisposition to RA; and to analyze the correlation between the gene polymorphisms included in the study and the production of anti-cyclic citrullinated peptide antibodies (ACCPA) and IgM rheumatoid factor (RF).Subjects and methods. The investigation was conducted within the framework of the «Early arthritis: Diagnosis, outcome, criteria, active treatment program». The prospective follow-up study included 122 patients with RA fulfilling the 1987 American College of Rheumatology (ACR) criteria; with disease duration of ≤ 2 years. 73 (59.8%) patients were included during the first 6 months after the onset of the disease. 74 (60.7%) and 81 (66.5%) patients were found to be positive for ACCPA and IgM RF, respectively. 314 healthy blood donors served as a control group. A real-time polymerase chain reaction was used in the patients and control individuals to study the distribution of the polymorphic variants of PTPN22 (+1858 C >T, rs2476601), TNFAIP3 (rs675520, rs6920220, rs10499194), CTLA4 (+49A>G, rs231775 ), TNFА (-308A>G, rs1800629), IL6 (-174G>C, rs1800795), IL6R (+358A>C, rs8192284), IL10 (-592A>C, rs1800872, -1082 A>G, rs1800896), MCP1/CCL2 (+2518A>G, rs1024611), and ICAM1 (721G>A, rs1799969) genes. Results and discussion. This analysis revealed an association of PTPN22 (+1858 C >T, rs2476601) and TNFAIP3 (rs675520, rs10499194) polymorphisms with the risk of RA (odds ratio (OR), 1.5; 95% confidence interval (CI), 1.0–2.3; p = 0.05; OR, 1.5; 95% CI, 1.1–2.0; p = 0.02; OR, 0.5; 95% CI, 0.4–0.8; p = 0.01, respectively. Further, there was a tendency towards a positive association of TNFAIP3 (rs6920220) and IL6R (rs8192284) polymorphisms with a predisposition to RA (p = 0.056). IL6 (rs1800795), IL10 (rs1800872, rs1800896), MCP1/CCL2 (rs1024611), and ICAM1 (rs1799969) polymorphisms were not associated with the risk of RA. An analysis of the findings after patient stratification by ACCPA and IgM RF (a binary variable) showed that none of the polymorphisms in question was associated with RF state. At the same time, PTPN22 (rs2476601), TNFAIP3 (rs675520), TNFAIP3 (rs10499194), and TNFА (rs1800629) polymorphisms were found to be significantly related to ACCPA state (a binary variable). The level of ACCPA as a quantitative variable was statistically significantly associated with CTLA4 (rs231775) and TNFА (rs1800629) polymorphisms in a dose-dependent fashion (р = 0.025 and р = 0.015, respectively). There was a marked tendency towards an association of ACCPA levels and IL6R gene polymorphism (p = 0.07). IL6 (rs1800795), IL10 (rs1800872, rs1800896), MCP1/CCL2 (rs1024611), and ICAM1 (rs1799969) polymorphisms were not correlated with ACCPA state (binary and quantitative variables).Conclusion. The findings suggest that a number of genes are implicated in the pathogenesis of RA and that they are involved in the development of ACCPA-positive and ACCPA-negative RA subtypes. No relationship was found between the production of IgM RF and the polymorphisms of the genes under study. The findings suggest that there appears to be different mechanisms for the formation of autoantibodies (ACCPA and IgM RF) in RA.

Background. The early diagnosis of ovarian cancer (OC) is an important problem in modern gynecological oncology due to significant detection rates for late-stage tumors. Intensive screening of patients from high-risk groups that include OC predisposition gene mutation carriers is indicated.Subjects and methods. An unselected group of 202 patients with OC and two control groups of blood donors: 591 healthy females; 1197 persons (including 591 females, 606 males) were examined. Patients and healthy individuals who identified themselves as ethnic Russians and residents of the Russian Federation participated in the study. Whole peripheral blood samples were collected at the Clinical Subdivisions of the N.N. Blokhin Russian Cancer Research Center and at the Department of Transfusiology of the Acad. B.V. Petrovsky Russian Research Center of Surgery in 2012–2013. Informed consent was obtained from all the participants. DNA was extracted using a Prep-GS-Genetics reagent kit. Real-time polymerase chain reaction genotyping assay was carried out by melting-curve analysis employing an BRCA SNP genotyping kit(BRCA1 and BRCA2 gene mutations) and original oligonucleotides (CHEK2, NBN, and BLM gene mutations). Thirteen population-specific mutations, including 7 (185delAG, 4153delA, 5382insC, 3819delGTAAA, 3875delGTCT, 300T>G, and 2080delA) in the BRCA1 gene, 1 (6174delT) in the BRCA2 gene, 3 (1100delC, IVS2+1G>A, and 470T>C) in the CHEK2 gene, 1 (657delACAAA) in the NBN gene, and 1 (1642C>T) in the BLM gene, were genotyped. Polymerase chain reaction was performed using a DTprime real-time detection thermal cycler.Results and discussion. BRCA1 and BRCA2 gene mutations were detected in 46 (22.8 %) patients with OC; the prevailing mutation in the BRCA1 gene was 5382insC (58.7 %). OC was diagnosed in 32.6 % of the patients aged 51 years or older. The rate of moderate-penetrance mutations (1100delC and IVS2+1G>A in the CHEK2 gene, 657del5 in the NBN gene, and 1642C>T in the BLM gene) was 0.5–1.0 % in the group of OC patients and 0–0.3 % in the control group of healthy women. The majority of these patients (5/6) were diagnosed with OC at age less than 50 years. The CHEK2 mutation, 470T>C, was more frequently encountered in the control group (6.6 %) than in the OC patient group (5.0 %). High rate of the CHEK2 mutation, IVS2+1G>A, was first shown for OC patients in the Russian Federation, the odds ratio was 11.9 (95 % confidence interval, 9.5–14.3; p = 0.056). It was preliminarily concluded that it played an important role in the development of OC in the Russian population; our findings should be verified in further investigations. The difference in the rate of mutations, such as 1100delC, IVS2+1G>A and 470T>C in the CHEK2 gene, 657del5 in the NBN gene, 1642C>T in the BLM gene, were insignificant in the patient and control groups, which may be related to the low population rate of these genetic markers and, in case of the CHEK2 mutation, 470T>C, may be linked to its low penetrance. By taking into account the fact that numerous studies have proven the clinical significance of all examined moderate-penetrance mutations whose prevalence in the Russian population has been confirmed by the authors of this paper, the inclusion of the mutations in a diagnostic panel to detect hereditary predisposition to OC is substantiated. The associated risks are higher for the rare mutations leading to the formation of truncated nonfunctional proteins, which are 1100delC and IVS2+1G>A in the CHEK2 gene, 657del5 in the NBN gene, and 1642C>T in the BLM gene. The penetrance of the CHEK2 mutation, 470T>C, is lower, which should be kept in mind during medical genetic counselling.Conclusion. The total rate of mutations in the BRCA1, BRCA2, CHEK2, NBN, and BLM genes in patients with OC was 30.7 %, which determines the expediency of molecular genetic screening in this category of patients.

The viral nature of many female genital cancers is now beyond question. By taking into account this fact, the problem of qualitative assessment ofthenatureofcervicalintraepithelialneoplasia(CIN)anditsfocusonprogressiontoinvasivecarcinomabecomesquitenatu ral.Studiesof a number of biological markers of carcinogenesis have recently provided a possibility for prospective prediction. The paper con siders the as- pects of importance of the molecular biological markers of proliferation and apoptosis in the etiopathogenesis of genital cancers. It gives the results of examinations of 16 patients with histologically verified squamous cell carcinoma of the cervix uteri, 40 patients di agnosed as having CIN of different grades (CIN-1, CIN-2, CIN-3 — squamous cell carcinoma in situ), and 6 patients with the morphologically unaltered cervi- calepithelium,whosecervicalscrapeswereanalyzedfortheexpressionofthemRNAgenesССNB1,Ki-67,BA G,BCL-2,ESR1,andPRG. It is shown that the molecular genetic findings may be new prognostic markers that reflect the possible disease developmental pathways, sug- gesting the need for further investigation of biomarkers in order to prevent malignancies and to reduce their morbidity.

Abstract. An imbalance between pro- and anti-inflammatory cytokine synthesis plays a crucial role in pathogenesis of rheumatoid arthritis (RA), including erosive joint lesions. Differences in cytokine profiles of RA patients are sufficiently investigated. However, possible interrelations between cytokine profile, immune inflammation, RA progression, and the disease prognosis require further investigations. Due to active search for novel targets in anti-cytokine therapy of RA, evaluation of cytokine levels in peripheral blood and synovial joint fluid remain quite relevant. Therefore, novel methods aimed to determine mRNA expressed by cytokine genes are thought to be promising. Our research was intended to develop test systems for quantitative determination of mRNAs for the following cytokines: TNFα, IL-1β, IL-6, IL-8, IL-17, IL-15, IL-10, IFNγ, IL-4, IL-2. Present article concerns specificities of the developed test systems, description of their technical principles, as well as comparative studies of cytokine gene expression in peripheral blood and synovial joint fluid in RA patients. (Med. Immunol., 2008, vol. 10, N 6, pp 563-570).

Introduction: The specialists refer unexplained infertility to the so-called diagnosis of exclusion due to the fact that in the process of medical examination of married couples the causes of infertility cannot be established. Material and methods: The clinical characteristics and embryological features of in vitro fertilization programs of couples with unexplained infertility versus the patients with tuboperitoneal infertility were analyzed retrospectively and prospectively. The study group comprised 93 women, who underwent 108 in vitro fertilization programs, and the control group consisted of 45 patients, who underwent 49 in vitro fertilization programs. Results: Significant differences (p<0.05) were found between the groups in anamnestic, clinical, laboratory, and instrumental characteristics. The ovarian stimulation protocols were comparable between the groups of patients. The blastulation rate was considered to be the endpoint in in vitro fertilization programs, and it was significantly lower in the group of women with unexplained infertility (45.53%). In-depth analysis of the embryonic stage of in vitro fertilization programs showed, that low blastulation rate in unexplained infertility was mainly due to the fact that embryos stopped developing about three days after they were cultured. At the same time the morphological assessment showed that the quality of blastocysts was higher in the group of unexplained infertility (66.7%) compared to the group of tuboperitoneal factor of infertility (45.8%). Preimplantation genetic testing for aneuploidy showed similar frequency of detection of euploid embryos (41.7% and 40.0%, respectively). Conclusion: A "clinical portrait" of women with unexplained infertility was described. The low blastulation rate was noted in in vitro fertilization programs for women with unexplained infertility. Given the identified impairments of early embryonic development in unexplained infertility, it is appropriate to recommend the patients to undergo early use of in vitro fertilization with good-quality embryo transfer (>3, AA, AB, BA according to Gardner grading system) on day 5-6 of culture without long-lasting preliminary examination and empirical treatment. [ABSTRACT FROM AUTHOR]

Aim. To identify gene polymorphisms (OPG, RANKL, VDR, SOST) and evaluate their relationship with bone mineral density (BMD) and fractures for further optimization of diagnosis and treatment of postmenopausal osteoporosis (PMO). Materials and methods. The study included 236 postmenopausal women living in Moscow and the Moscow region. The main group (I) consisted of 174 patients, aged 50 to 83 years, with BMD < - 2.5 SD for the T-score. The comparison group (II) consisted of 62 postmenopausal women with BMD within the normal range and the lack of previous fractures, aged 50 to 77 years. Molecular genetic analysis of polymorphisms of VDR (rs10735810, rs1544410), RANKL (rs9594738, rs9594759) and OPG (rs3102735, rs3102735 and rs4355801), SOST (rs1230399) was performed by polymerase chain reaction in all subjects with PMO and in the control group. Results. In the presence of the T allele of the gene RANKL (rs9594759 and rs9594738) risk of reduced BMD at L1-L4 was increased by 2 times. Women with genotype C/C gene polymorphism of OPG (rs3102735) the risk of fractures of the distal radius (PR) was increased by 17 times, regardless of BMD. Genotype G/G rs1544410 polymorphism of VDR gene in patients with PMO is associated with an increased risk of fractures of the distal radius by three times. In patients with PMO genotype C/C in gene SOST (rs1230399) only cause differences in body mass index. According to an autosomal recessive pattern, homozygous genotype C/C was significantly associated with obesity in the PMO. Conclusions. Polymorphisms of genes RANKL (rs9594759 and rs9594738), OPG (rs3102735) and VDR (rs1544410) are associated with the risk of fractures and PMO. Gene SOST (rs1230399) had no statistically significant effect on BMD and fracture risk.

Цель: Изучить эффективность золедроновой кислоты в терапии постменопаузального остеопороза (ПМО) с учетом полиморфизма гена фарнезилдифосфат-синтетазы (FDPS). Методы исследования: клинический, определение биохимических маркеров костного метаболизма (БМКР) - электрохемилюминесцентным методом («Хоффманн-Ла Рош ЛТД», Швейцария). Измерение МПК проводили с помощью двухэнергетической рентгеновской абсорбциометрии позвонков поясничной области (L1-L4) и шейки бедренной кости (Neck left, Neck total left). Молекулярно-генетический (определение однонуклеотидного полиморфизма гена FDPS (rs2297480) - методом «примыкающих проб» с анализом кривых плавления (ЗАО «НПФ ДНК-Технология, Россия)). Результаты. Обследовано 225 женщин с постменопаузальным остеопорозом. Средний возраст составил 59 (5466) лет. Средняя продолжительность периода постменопаузы 7 (2-13) лет. ИМТ=27,2(23,6-29,05) кг/м2. Распределение аллелей (АА:АС:СС) составило 55,1(n=144):39,5(n=103):5, 4(n=14). Базальные уровни биохимических маркеров костного ремоделирования (БМКР) соответствовали периоду постменопаузы и статистически значимо не различались в зависимости от генотипа FDPS. Средние показатели МПК в поясничном отделе позвоночника и/или шейке бедра соответствовали остеопорозу. Всем пациенткам проводили терапию золедроновой кислотой (zol) в дозе 5 мг в виде внутривенной инфузии 1 раз в 12 месяцев в течение 2 лет. Дополнительно все пациенты получали кальций 1000 мг/сут и витамин Д3 800МЕ/сут. Реакция БМКР на инфузию zol различалась в зависимости от генотипа FDPS. Через 6 месяцев после 1-ой инфузии достоверно более выраженное снижение B-Crosslaps 92 (91-93)% отмечено у пациентов с С/С генотипом (p=0,056), по сравнению с 82% у носителей аллеля А (p=0.07). Через 9 месяцев после инфузии B-Crosslaps у носителей аллеля А повышались до 75%, остеокальцина - 44,4% от исходного. Тогда как у носителей генотипа C/C как B-Crosslaps - (87%), так и osteocalcine -(53,6%) оставались по-прежнему низкими (р=0,056). К 12 месяцу после инфузии уровни B-Crosslaps и osteocalcin у носителей аллеля A повышались и соответствовали премено-паузальным значениям, тогда как у носителей С/С генотипа оставались в пределах ниже нижней границы нормы для пременопаузы. У пациентов с СС генотипом на фоне выраженного снижения БМКР после 2ой инфузии золедроновой кислоты произошло снижение МПК на 5,6%. Выводы. Различная реакция на терапию золедроновой кислотой у пациенток с ПМО связана с полиморфизмом гена FDPS (rs2297480). Для пациентов с генотипом С/С характерно «гиперторможение» костного обмена в ответ на терапию золедроновой кислотой, что возможно, было причиной отрицательной динамики МПК в поясничном отделе позвоночника на втором году терапии золедроновой кислотой.

Conclusion. 1. There were no significant differences in the occurrence frequency of allele and genotypes of C1444 locus of CRP gene in patient with osteoporosis. 2. It was founded that T allele and TT genotype of C1846T locus of CRP gene were more common in women with osteoporosis. 3. The determination of gene CRP polymorphism gives a responsibility to realize individual prognosis and to take preventive measures. Цель исследования. Определить полиморфизмы генов OPG, RANKL, VDR, SOST и оценить их взаимосвязь с минеральной плотностью кости (МПК) и переломами для последующей оптимизации диагностики и лечения постменопаузального остеопороза. Материал и методы. В исследование вошли 236 женщин в постменопаузе, проживающих в Москве и Московской области. Основную группу составили 174 пациентки, в возрасте от 50 до 83 лет, с показателями минеральной плотности кости (МПК) < - 2,5 SD по Т-критерию. Группу сравнения составили 62 женщины в постменопаузе с показателями МПК в пределах нормальных значений и отсутствием переломов в анамнезе, в возрасте от 50 до 77 лет. В нашем исследовании всем испытуемым с постменопаузальным остеопорозом и группы контроля с помощью полимеразной цепной реакции проводили молекулярногенетическое проводили с определением полиморфизмов генов VDR(rs10735810, rs1544410), RANKL (rs9594738, rs9594759) и OPG (rs3102735, rs3102735 и rs4355801), SOST (rs1230399). Результаты. При наличии Т аллелей гена RANKL по полиморфизмам rs9594759 и rs9594738 риск снижения МПК в поясничном отделе позвоночника увеличивается в 2 раза. У женщин с гомозиготным генотипом С/С по полиморфизму rs3102735 гена OPG риск развития переломов дистального отдела лучевой кости повышается в 17 раз вне зависимости от показателей МПК. Наличие генотипа G/G по полиморфизму rs1544410 гена VDR у пациенток с постменопаузальным остеопорозом ассоциировано с повышением риска переломов дистального отдела лучевой кости в 3 раза. У пациенток с ПМО гомозиготный генотип С/С по полиморфизму rs1230399 гена SOST обуславливают только различия в индексе массы тела. Заключение. Полиморфизмы генов RANKL (rs9594759 и rs9594738), OPG (rs 3102735) и гена VDR(rs1544410) ассоциированы с риском развития постменопаузального остеопороза и переломов. Ген SOST(rs1230399) не оказывает статистически значимого влияния на МПК и риск переломов.