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Shvangiradze T.A.,Endocrinology Research Center | Bondarenko I.Z.,Endocrinology Research Center | Troshina E.A.,Endocrinology Research Center | Shestakova M.V.,Moscow State University | And 7 more authors.
Obesity and Metabolism | Year: 2016

Introduction. Cardiovascular disease (CVD) remain the leading cause of death in industrialized countries. Patients with coronary heart disease (CHD) in combination with diabetes mellitus type 2 (T2DM) are characterized by more severe CHD and poor prognosis. Resent data indicate microRNAs (miRNAs) as important participants in the pathogenesis of various pathological conditions, including obesity, T2DM and CVD. The aim of this study was to determine expression of miRNAs associated with the development of CHD, and transforming growth factor beta (TGF-ß) in a patients with T2DM and obesity Materials and methods. 42 patients with 1-2 degrees obesity and diagnosed T2DM were divided into 2 groups. The first group with CHD, the second group - without CHD. 9 miRNAs were evaluated: miRNA-1, miRNA- 21, miRNA-26a, m miRNA-27, miRNA-33a, miRNA-33b, miRNA-133a, miRNA-133b, miRNA-208. Results and discussion. Significant differences were found in expression of miRNA-21, miRNA-26a, miRNA27a. An increased expression of miRNA-21, miRNA-27a was found in patients CHD while the expression of miRNA-26a was reduced in comparison with the group without CHD. Conclusion. The results of this study may be an initial step for the detection of molecular basis in CHD pathogenesis in these patients by quantifying miRNA expression.


Lavrov A.V.,Russian National Research Medical University | Smirnikhina S.A.,Federal State Budgetary Institution Research Center for Medical Genetics | Adilgereeva E.P.,Federal State Budgetary Institution Research Center for Medical Genetics | Kutsev S.I.,Russian National Research Medical University
BMC Genetics | Year: 2016

Background: Genome variability of host genome and cancer cells play critical role in diversity of response to existing therapies and overall success in treating oncological diseases. In chronic myeloid leukemia targeted therapy with tyrosine kinase inhibitors demonstrates high efficacy in most of the patients. However about 15 % of patients demonstrate primary resistance to standard therapy. Whole exome sequencing is a good tool for unbiased search of genetic variations important for prognosis of survival and therapy efficacy in many cancers. We apply this approach to CML patients with optimal response and failure of tyrosine kinase therapy. Results: We analyzed exome variations between optimal responders and failures and found 7 variants in cancer-related genes with different genotypes in two groups of patients. Five of them were found in optimal responders: rs11579366, rs1990236, rs176037, rs10653661, rs3803264 and two in failures: rs3099950, rs9471966. These variants were found in genes associated with cancers (ANKRD35, DNAH9, MAGEC1, TOX3) or participating in cancer-related signaling pathways (THSD1, MORN2, PTCRA). Conclusion: We found gene variants which may become early predictors of the therapy outcome and allow development of new early prognostic tests for estimation of therapy efficacy in CML patients. Normal genetic variation may influence therapy efficacy during targeted treatment of cancers. © 2015 Lavrov et al.


Smirnikhina S.A.,Federal State Budgetary Institution Research Center for Medical Genetics | Lavrov A.V.,Russian National Research Medical University | Chelysheva E.Y.,Federal State Funded Institution National Research Center for Hematology of the Ministry of Healthcare of the Russian Federation | Adilgereeva E.P.,Federal State Budgetary Institution Research Center for Medical Genetics | And 3 more authors.
Leukemia and Lymphoma | Year: 2016

Chronic myeloid leukemia (CML) is a myeloproliferative disease well treated by tyrosine kinase inhibitors (TKIs). The aim was to identify genes with a predictive value for relapse-free survival after TKI cessation in CML patients. We performed whole-exome sequencing of DNA from six CML patients in long-lasting deep molecular remission. Patients were divided into two groups with relapse (n = 3) and without relapse (n = 3) after TKI discontinuation. We found variants in genes CYP1B1, ALPK2, and IRF1 in group of patients with relapse and one variant in gene PARP9 in group of patients without relapse. We verified prognostic value of the found markers in a small group of patients with TKI discontinuation and demonstrated their high sensitivity (77%), specificity (86%), positive (85%), and negative (79%) predictive values. Thus we revealed genetic variants, which are potential markers of outcome prediction in CML patients after TKI discontinuation. © 2016 Taylor & Francis


Munck A.,University Paris Diderot | Alberti C.,Clinical Epidemiology Unit | Alberti C.,University Paris Diderot | Alberti C.,French Institute of Health and Medical Research | And 8 more authors.
Journal of Cystic Fibrosis | Year: 2016

Background Distal intestinal obstruction syndrome (DIOS) is a specific complication of cystic fibrosis. Methods A study was performed in 10 countries to prospectively evaluate the incidence, associated factors, and treatment modalities in children and adults. Results 102 patients presented 112 episodes. The incidence of DIOS was similar in children and adults. Medical treatment failed only in cases of complete DIOS (11%). Children with meconium ileus had a higher rate of surgery for DIOS (15% vs. 2%, p = 0.02). Complete DIOS entailed longer hospitalisation (4 [3; 7] days vs. 3 [1; 4], p = 0.002). Delayed arrival at hospital and prior weight loss had a significant impact on the time needed for DIOS resolution. Associated CF co-morbidities for DIOS included meconium ileus (40% vs. 18%, p < 0.0001), exocrine pancreatic insufficiency (92% vs. 84%, p = 0.03), liver disease (22% vs. 12%, p = 0.004), diabetes mellitus (49% vs. 25%, p = 0.0003), and Pseudomonas aeruginosa (68% vs. 52%, p = 0.01); low fibre intake and insufficient hydration were frequently observed. Female gender was associated with recurrent DIOS (75% vs. 52%, p = 0.04), constipation with incomplete episodes (39% vs. 11%, p = 0.03), and poor patient compliance in taking pancreatic enzyme therapy during complete episodes (25% vs. 3%, p = 0.02). Conclusion DIOS is a multifactorial condition having a similar incidence in children and adults. We show that delayed arrival at hospital after the initial symptoms causes significant morbidity. Early recognition and treatment would improve the prognosis. © 2016 European Cystic Fibrosis Society.


Zernov N.,Federal State Budgetary Institution Research Center for Medical Genetics | Skoblov M.,Russian National Research Medical University | Baranova A.,George Mason University | Baranova A.,Atlas Biomedical Group | Boyarsky K.,Genesis Centre
Reproductive Biology and Endocrinology | Year: 2016

Background: Anomalous levels of gonadotropin-releasing hormone (GnRH) secretion result in a variety of reproductive phenotypes associated with infertility or subfertility. The normosmic isolated hypogonadotropic hypogonadism (nIHH) is due to a failure of either GnRH pulsatile secretion in hypothalamus or its reception in pituitary. The spectrum of nIHH-associated alterations continues to expand, especially when additional ethnic populations are investigated. The aim of this study was to uncover genetic causes for nIHH in patients of Russian origin. Methods: For two nIHH patients referred to infertility clinic, both exons and promoter sequences of 6 GnRH signaling genes were sequenced. Results: Patient 1 was a compound heterozygote for mutations in GnRH and its receptor encoding genes, while in Patient 2 GnRHR mutations were found in homozygous state. In both patients, the coding frame of GnRHR gene harbored missense-mutation Arg139His previously described as founder mutation in Polish and Brazilan patients. IVF/ET treatments were successful, with phenotypically healthy offsprings delivered. Conclusion: Polish founder mutation Arg139His in GnRHR was found in two nIHH patients originating from Western region of Russia. Common variant of GnRH-encoding gene, Trp16Ser, could possibly contribute to reproductive phenotypes in patients with heterozygous mutations of other GnRH signaling pathway genes. © 2016 The Author(s).


PubMed | Federal State Budgetary Institution Research Center for Medical Genetics and Genesis Centre
Type: Journal Article | Journal: Reproductive biology and endocrinology : RB&E | Year: 2016

Anomalous levels of gonadotropin-releasing hormone (GnRH) secretion result in a variety of reproductive phenotypes associated with infertility or subfertility. The normosmic isolated hypogonadotropic hypogonadism (nIHH) is due to a failure of either GnRH pulsatile secretion in hypothalamus or its reception in pituitary. The spectrum of nIHH-associated alterations continues to expand, especially when additional ethnic populations are investigated. The aim of this study was to uncover genetic causes for nIHH in patients of Russian origin.For two nIHH patients referred to infertility clinic, both exons and promoter sequences of 6 GnRH signaling genes were sequenced.Patient 1 was a compound heterozygote for mutations in GnRH and its receptor encoding genes, while in Patient 2 GnRHR mutations were found in homozygous state. In both patients, the coding frame of GnRHR gene harbored missense-mutation Arg139His previously described as founder mutation in Polish and Brazilan patients. IVF/ET treatments were successful, with phenotypically healthy offsprings delivered.Polish founder mutation Arg139His in GnRHR was found in two nIHH patients originating from Western region of Russia. Common variant of GnRH-encoding gene, Trp16Ser, could possibly contribute to reproductive phenotypes in patients with heterozygous mutations of other GnRH signaling pathway genes.


PubMed | Federal State Funded Institution National Research Center for Hematology of the Ministry of Healthcare of the Russia and Federal State Budgetary Institution Research Center for Medical Genetics
Type: | Journal: BMC genetics | Year: 2016

Genome variability of host genome and cancer cells play critical role in diversity of response to existing therapies and overall success in treating oncological diseases. In chronic myeloid leukemia targeted therapy with tyrosine kinase inhibitors demonstrates high efficacy in most of the patients. However about 15 % of patients demonstrate primary resistance to standard therapy. Whole exome sequencing is a good tool for unbiased search of genetic variations important for prognosis of survival and therapy efficacy in many cancers. We apply this approach to CML patients with optimal response and failure of tyrosine kinase therapy.We analyzed exome variations between optimal responders and failures and found 7 variants in cancer-related genes with different genotypes in two groups of patients. Five of them were found in optimal responders: rs11579366, rs1990236, rs176037, rs10653661, rs3803264 and two in failures: rs3099950, rs9471966. These variants were found in genes associated with cancers (ANKRD35, DNAH9, MAGEC1, TOX3) or participating in cancer-related signaling pathways (THSD1, MORN2, PTCRA).We found gene variants which may become early predictors of the therapy outcome and allow development of new early prognostic tests for estimation of therapy efficacy in CML patients. Normal genetic variation may influence therapy efficacy during targeted treatment of cancers.


PubMed | Federal State Budgetary Institution Research Center for Medical Genetics and Moscow State University
Type: | Journal: Andrologia | Year: 2016

The fibrous sheath is a unique cytoskeletal structure surrounding the axoneme and outer dense fibres of the sperm flagellum. Dysplasia of the fibrous sheath (DFS) is a defect of spermatozoa observed in severe asthenozoospermic patients and characterised by morphologically abnormal flagella with distorted fibrous sheaths. Sperm-specific glyceraldehyde-3-phosphate dehydrogenase (GAPDS) is a glycolytic enzyme that is tightly associated with the fibrous sheath of the sperm flagellum. The enzymatic activity of GAPDS was investigated in sperm samples of seven patients with DFS and compared to that of normal spermatozoa (n=10). The difference in GAPDS activity in DFS and normal spermatozoa was statistically significant (0.190.11 and 0.750.11mol NADH per min per mg protein respectively). Immunochemical staining revealed irregular distribution of GAPDS in the flagellum of DFS spermatozoa. Other five samples with typical alterations in the fibrous sheath were assayed for mutations within human GAPDS gene. In all five cases, a replacement of guanine by adenine was revealed in the intron region between the sixth and the seventh exons of GAPDS. It is assumed that the deficiency in GAPDS observed in most DFS sperm samples is ascribable to a disorder in the regulation of GAPDS expression caused by the mutation in the intron region of GAPDS gene.


PubMed | Moscow Institute of Physics and Technology, Federal State Budgetary Institution Research Center for Medical Genetics, Russian National Research Medical University, Niigata University and Social Republic
Type: Journal Article | Journal: The Journal of investigative dermatology | Year: 2016

Hypotrichosis is an abnormal condition characterized by decreased hair density and various defects in hair structure and growth patterns. In particular, in woolly hair, hypotrichosis is characterized by a tightly curled structure and abnormal growth. In this study, we present a detailed comparative examination of individuals affected by autosomal-recessive hypotrichosis (ARH), which distinguishes two types of ARH. Earlier, we demonstrated that exon 4 deletion in the lipase H gene caused an ARH (hypotrichosis 7; MIM: 604379) in populations of the Volga-Ural region of Russia. Screening for this mutation in all affected individuals revealed its presence only in the group with the hypotrichosis 7 phenotype. Other patients formed a separate group of woolly hair-associated ARH, with a homozygous missense mutation c.712G>T (p.Val238Leu) in a highly conserved position of type I keratin KRT25 (K25). Haplotype analysis indicated a founder effect. An expression study in the HaCaT cell line demonstrated a deleterious effect of the p.Val238Leu mutation on the formation of keratin intermediate filaments. Hence, we have identified a previously unreported missense mutation in the KRT25 gene causing ARH with woolly hair.

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