Occupational bronchial asthma caused by exposure to polyvinyl chloride: phenotypes of the disease

2019 ◽  
pp. 14-18 ◽  
Author(s):  
Olga S. Vasilyeva ◽  
Lyudmila P. Kuzmina ◽  
Maria M. Kolyaskina
Keyword(s):  
Polyvinyl Chloride ◽  
Bronchial Asthma ◽  
Molecular Genetic ◽  
Null Alleles ◽  
Pvc Membrane ◽  
Processing Plant ◽  
Multifactorial Disease ◽  
Glutathione S Transferase ◽  
Genetic Studies ◽  
Genetic Characteristics

Introduction.Mechanism underlying development of occupational bronchial asthma (OA) caused by exposure to polyvinyl chloride (PVC) aerosols is not completely clear. Complex properties of PVC aerosols components indicate possible development of OA among workers via both non-immune and immune mechanisms.Objectiveis to study clinical and genetic characteristics of occupational bronchial asthma development at meat packers’ workplace.Materials and methods.Examination covered 113 male and female meat-processing plant workers. A group (48 people) appeared to have daily contact with toxic-allergenic aerosols which were released as a smoke into the working area from molten PVC membrane during the meat products packing. All the examinees underwent clinical and functional tests of bronchopulmonary system and molecular genetic studies: identification of hyposecretory alleles of α–1IP gene; determination of genetic polymorphism of GSTM1 and GSTT 1.Results and discussion.The study proved that exposure to PVC degradation products causes irritation and sensitization of the respiratory tract, visible mucous membranes and skin. The examinees with 5–10 years of service demonstrated reversible obstructive pulmonary ventilation disorders with bronchial hypersensitivity to occupational factors (30 people) and symptoms of bronchial asthma (18 people) of immune and non-immune origin. The asthma phenotypes were determined: occupational — immune and non-immune (11 people) and aggravated by work conditions (7 people). The study proved that individual risk factors of occupational bronchial asthma in meat-packers are: hyposecretory PiMZ variant of α1-PI gene and deletion of glutathione-S-transferase genes (GSTM1 and GSTT 1). The findings prove that meatpackers’ asthma is a multifactorial disease.Conclusion.Hyposecretory alleles of α1-PI gene appeared to participate in occupational bronchial asthma development. Identified relationships between hyposecretory variants of α1-PI gene, null alleles of glutathione-S-transferase genes (GSTM1 and GSTT 1) carriage, occupational bronchial asthma development and severity suggest that meat-packers’ asthma is a multifactorial disease. This could be an explanation of various phenotypes of occupational bronchial asthma. Problem of occupational bronchial asthma development due to influence of PVC pyrolysis products necessitates further wide clinical, hygienic and molecular genetic studies.

scholarly journals ROLE OF GENETIC PREDISPOSITION, GENE POLYMORPHISM OF GLUTATHIONE-S-TRANSFERASE (GSTT1, GSTM1, GSTP1) AND SOME ADVERSE FACTORS IN DEVELOPMENT OF BRONCHIAL ASTHMA IN CHILDREN – RESIDENTS OF RADIOACTIVELY CONTAMINATED AREAS

2021 ◽  
Vol 26 ◽  
pp. 449-463
Author(s):  
Ye. Stepanova ◽  
◽  
I. Kolpakov ◽  
V. Vdovenko ◽  
V. Zigalo ◽  
...  
Keyword(s):  
Gene Polymorphism ◽  
Bronchial Asthma ◽  
Gene Deletion ◽  
Molecular Genetic ◽  
Glutathione S Transferase ◽  
Genetic Studies ◽  
Hereditary Predisposition ◽  
Gstm1 Gene ◽  
Polymorphic Variants ◽  
Asthma In Children

Objective: to determine the influence of hereditary predisposition, polymorphism of GSTT1, GSTM1, GSTP1 genes and environmental factors on the development of bronchial asthma in children – residents of radioactively contaminated areas. Materials and methods. School-age children-residents of radioactively contaminated areas with bronchial asthma, and those without clinical signs of respiratory pathology were examined. Genetic, medical, biological and social risk factors were determined based on the study of anamnestic data and medical records. Ventilation lung capacity was assessed by the method of computer spirometry. Molecular genetic studies were carried out using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) for further analysis. Results. Molecular genetic studies of the distribution of genotypes and frequencies of polymorphic variants of the genes GSTT1, GSTM1, GSTP1 were performed in children living under long-term intake of 137Cs by food chains. It was found that in children with BA the tendency to frequency of the deletion variant of the GSTT1 and GSTM1 genes in comparison with children without bronchial and pulmonary pathology was increased. The study of distributing the GSTP1 A313G gene polymorphic variants revealed in children with BA a significant increase in the frequency of AG-genotype, compared with the data of reference group. Adverse factors that increase the risk of developing bronchoobstructive disorders and the probability of their implementation in the form of bronchial asthma in children residents of RCA have been identified. It is established that among them the leading role is played by hereditary predisposition to this disease. On the part of the child, such negative factors were unfavorable conditions of fetal development, the presence of signs of exudative-catarrhal diathesis, manifestations of allergies and frequent respiratory diseases from the first months of life. It was found that the risk of developing BA was significantly increased in children with the GSTT1 and GSTM1 gene deletion genotypes; an increased risk of developing BA in children with a combination of the GSTP1 A313G gene polymorphism with deletion polymorphism of the GSTT1 or GSTM1 gene was determined. Сonclusion. Оne of the leading mechanisms, due to which there is a realization of hereditary predisposition to bronchial asthma in children living under constant intake of radionuclides with a long half-life, is the polymorphism of certain glutathione-S-transferase genes, namely, GSTT1, GSTM1 and A313G gene deletion polymorphism and GSTP1 gene polymorphism. Key words: children, radioactively contaminated areas, risk factors, bronchial asthma, glutathione-S-transferase gene polymorphism.

Small Round Cell Tumors of Bone

2007 ◽  
Vol 131 (2) ◽  
pp. 192-204 ◽  
Author(s):  
Meera Hameed
Keyword(s):  
Molecular Genetic ◽  
Malignant Neoplasms ◽  
Round Cell ◽  
Genetic Studies ◽  
Genetic Characteristics ◽  
Small Round Cell ◽  
Ovid Medline ◽  
Tumors Of Bone ◽  
Round Cell Tumors ◽  
Ewing Family Tumors

Abstract Context.—Primary small round cell tumors of the bone are a heterogeneous group of malignant neoplasms presenting predominantly in children and adolescents. They include Ewing sarcoma/peripheral neuroectodermal tumor or Ewing family tumors, lymphoma, mesenchymal chondrosarcoma, and small cell osteosarcoma. Even though they share many morphological similarities, their unique biological and genetic characteristics have provided substantial insights into the pathology of these diverse neoplasms. Objective.—To provide an overview of the clinical, radiologic, pathologic, and genetic characteristics of these tumors along with a pertinent review of the literature. Data Sources.—A literature search using PubMed and Ovid MEDLINE was performed, and data were obtained from various articles pertaining to clinicopathologic, biological, and genetic findings in these tumors. Additionally, findings from rare cases have been included from author's subspecialty experience. Conclusion.—The diagnosis of small round cell tumors can be made accurately by applying clinicopathologic criteria, as well as a panel of immunohistochemical and genetic studies in appropriate cases. Molecular genetic studies may provide further insight into the biology, histogenesis, and prognosis of these tumors.

scholarly journals MOLECULAR GENETIC CHARACTERISTICS CHILDREN WITH GROWTHHORMONE DEFICIENCY

2017 ◽  
Vol 9 (4) ◽  
pp. 12-16
Author(s):  
O S Berseneva ◽  
A S Glotov ◽  
O S Glotov ◽  
E A Serebryakova ◽  
T E Ivashenko ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Genetic Studies ◽  
Genetic Characteristics ◽  
Therapeutic Algorithms ◽  
Congenital Hypopituitarism

Clinical manifestations of heterogeneity of growth hormone deficiency when definitive results of hormonal stimulus test determines the need to search for molecular genetic markers of the disease to form personalized therapeutic algorithms. Molecular genetic analysis in patients with congenital hypopituitarism was carried out by new-generation sequencing (NGS) with "Amplisek" technology. All patients with congenital hypopituitarism, who are in a special registry of Saint Petersburg, were included in this study. differences in the frequency of detection of mutations in patients with multiple anterior pituitary hormone deficiency and in patients with isolated growth hormone deficiency were found. The mutation frequency of diagnosis in genes responsible for congenital hypopituitarism in patients of St. Petersburg were studied.Mutations in genes associated with congenital hypopituitarism were identified in 16.3% of patients with pituitary dwarfism (16 of 98). The most commonly diagnosed mutations are changes in gene PROP1. In carrying out the molecular genetic studies of patients with congenital hypopituitarism is necessary to consider the likelihood of the presence of these rare pathologies such as loss of genes GHSR, ARNT2, BTK. Currently conducting molecular genetic studies in patients with congenital hypopituitarism further predicts development of the disease and, if necessary, adjust the ongoing replacement therapy.

scholarly journals MOLECULAR GENETIC ASPECTS OF BRONCHIAL HYPERREACTIVITY IN CHILDREN – RESIDENTS OF RADIOACTIVELY CONTAMINATED AREAS

2020 ◽  
Vol 25 ◽  
pp. 531-542
Author(s):  
Ye. Stepanova ◽  
◽  
I. Kolpakov ◽  
V. Vdovenko ◽  
V. Zigalo ◽  
...  
Keyword(s):  
Gene Deletion ◽  
Molecular Genetic ◽  
Bronchial Hyperreactivity ◽  
Glutathione S Transferase ◽  
Deletion Polymorphism ◽  
Genetic Studies ◽  
Gstm1 Gene ◽  
Lung Capacity ◽  
Transferase Gene ◽  
Gstp1 Gene

Objective. to determine the relationship between polymorphisms of glutathione S-transferase gene family and bronchial hyperreactivity in children living in radioactively contaminated areas. Materials and methods. School age children-residents of radioactively contaminated areas (RCA), without clinical signs of respiratory pathology were examined. Molecular genetic studies were carried out by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) for further analysis. The GSTT1, GSTM1 gene deletion polymorphism was investigated using multiplex PCR. PCR and PCR-RFLP analyses were performed in the study of the GSTP1 gene A313G polymorphism. The ventilation lung capacity was examined by the pneumotachographic method according to the analysis of «the flow–volume» loop. The pharmacologic inhalation test with bronchodilator drug, affecting the β2-adrenergic lung receptors was used to detect the early changes in the ventilation lung capacity – the bronchial hyperreactivity (latent and nonlatent bronchospasm). Results. Molecular genetic studies showed that the GSTM1 gene deletion genotype and the GSTP1 gene A313G polymorphism were found significantly more often in the subgroup of children with bronchial hyperreactivity living in RCA than in children without bronchial hyperreactivity and children of the control group. The frequency of GSTT1 deletion polymorphism did not have a statistically significant difference in all subgroups. Conclusions. The GSTM1 gene deletion polymorphism and the GSTP1 gene A313G genotype may be a risk factor for developing bronchial hyperreactivity in children living under adverse environmental conditions, including radioactively contaminated areas. Key words: children, radioactively contaminated areas, bronchial hyperreactivity, glutathione-S-transferase gene polymorphisms.

scholarly journals Clinical and molecular genetic characteristics of MODY1—3 cases in the Russian Federation as shown by NGS

2018 ◽  
Vol 63 (6) ◽  
pp. 369-378
Author(s):  
Natalya A. Zubkova ◽  
Olesya A. Gioeva ◽  
Yulia V. Tikhonovich ◽  
Vasily M. Petrov ◽  
Evgeny V. Vasilyev ◽  
...  
Keyword(s):  
Russian Federation ◽  
Clinical Presentation ◽  
Molecular Genetic ◽  
Inclusion Criteria ◽  
Genetic Studies ◽  
Genetic Characteristics ◽  
Synonymous Mutations ◽  
Endogenous Insulin ◽  
Hnf1a Gene ◽  
The Russian Federation

Objective — the research was aimed at studying clinical and molecular genetic characteristics of the most common subtypes of MODY (1—3) detected by NGS. Material and methods. The study included 312 patients (162 boys and 150 girls) aged 3 months to 25 years with suspected MODY. Inclusion criteria were as follows: carbohydrate metabolism disorders of varying severity, negative titer of ICA, IA2, and GAD autoantibodies, preserved secretion of endogenous insulin. NGS technique was used for molecular genetic studies. Custom DNA Panel was used for the multiplex PCR and sequencing using the Ion Ampliseq technique. Custom Diabetes Panel included 28 genes (13 MODY candidates genes and other diabetes-associated genes). Non-synonymous mutations that were not previously described were rated as «probably pathogenic» if they had minor allele frequency of <0.1% and «pathogenic» when assessed against the ANNOVAR database. Results. Mutations in MODY candidate genes were detected in 178 (57.1%) probands. Of these, 99 mutations in GCK99 gene were found in 129 (41.4%) probands and 77 relatives, 20 mutations in HNF1A gene were found in 19 (6.1%) probands and 14 relatives, 8 mutations in HNF4A gene — in 9 (2.9%) probands and 3 relatives. All detected mutations were heterozygous. MODY1 subtype was not previously described in the Russian Federation. Conclusions. The Russian population is dominated by MODY2 subtype. Only MODY2 is characterized by typical clinical presentation. NGS is a highly effective method in the diagnosis of MODY.

Clinical, hormonal, and molecular-genetic characteristics of two cases of abnormal sex formation (ASF) in 46XY subjects caused by type 3 17-beta hydroxysteroid dehydrogenase deficiency

2011 ◽  
Vol 57 (3) ◽  
pp. 25-30
Author(s):  
A A Kolodkina ◽  
N Iu Kalinchenko ◽  
A N Nizhnik ◽  
M A Nokel' ◽  
A N Tiul'pakov
Keyword(s):  
Dehydrogenase Deficiency ◽  
Molecular Genetic ◽  
External Genitalia ◽  
Hydroxysteroid Dehydrogenase ◽  
Rare Form ◽  
Intrauterine Development ◽  
Genetic Studies ◽  
Genetic Characteristics ◽  
Sex Development ◽  
Type 3

Type 3 17-beta hydroxysteroid dehydrogenase (17HSD3) deficiency is a rare form of abnormal sex formation (ASF) in 46XY subjects in which the conversion of androstendione to testosterone is blocked; this defect results in compromised masculinization of the external genitalia during the intrauterine development. A distinctive feature of this form of sex development is masculinization at puberty due to the extragonadal conversion of androstendione to testosterone. Two clinical cases are reported: both girls were born with the female-type of external genitalia and 46XY karyotype, but progressive virilization in the pubertal period gave reason to suspect diagnosis of 17HSD3 deficiency. In both cases, this diagnosis was confirmed in molecular genetic studies (the following mutations were identified in the HSD17B3 gene: c.728-734delGATAACCp.1244fsX254/c.277+4A>T and c.277+4A>T). These two cases are the first reports of 17HSD3 deficiency in the Russian literature.

scholarly journals Congenital hypopituitarism in children. Molecular-genetic characteristics

2018 ◽  
Vol 10 (1) ◽  
pp. 49-54
Author(s):  
O. S. Berseneva ◽  
A. S. Glotov ◽  
O. S. Glotov ◽  
E. A. Serebryakova ◽  
T. E. Ivashenko ◽  
...  
Keyword(s):  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Genetic Studies ◽  
Genetic Characteristics ◽  
Saint Petersburg ◽  
Stimulation Tests ◽  
New Generation Sequencing ◽  
New Generation ◽  
Congenital Hypopituitarism ◽  
Growth Hormone Insufficiency

In connection with the ambiguity in the interpretation of the results of stimulation tests in congenital hypopituitarism, children need to search for molecular genetic markers of the disease. Molecular genetic analysis in patients with congenital hypopituitarism (genes GH1, GHRH, GHRHR,BTK, GHSR, PROP1, POU1F1, HESX1, LHX3, LHX4, SOX3, SOX2, OTX2, GLI2, ARNT2, ARPC5L, DLK1, DRD2, PAX6, RNPC3, SHH, SPCS2, SPCS3), was carried out by new-generation sequencing (NGS) with “Amplisek” technology. All patients with congenital hypopituitarism, who are in a special registry of Saint Petersburg, were included in this study. A difference in the incidence of mutations in patients with multiple deficiency of adenohypophysis hormones (27.7%) and in patients with isolated growth hormone insufficiency (9.6%) was revealed. The mutation frequency of diagnosis in genes responsible for congenital hypopituitarism in patients of Saint Petersburg were studied. Mutations in genes associated with congenital hypopituitarism were identified in 16.3% of patients with pituitary dwarfism (16 of 98). The most commonly diagnosed mutations are changes in gene PROP1. In carrying out the molecular genetic studies of patients with congenital hypopituitarism is necessary to consider the likelihood of the presence of these rare pathologies such as loss of genes GHSR, ARNT2, BTK. Currently conducting molecular genetic studies in patients with congenital hypopituitarism further predicts development of the disease and, if necessary, adjust the ongoing replacement therapy.

Clinical application of polymorphic variants of the genes ESR1 and CYP2D6*4 in patients with breast and endometrial cancer

2017 ◽  
pp. 132-138
Author(s):  
O.V. Paliychuk ◽  
◽  
L.Z. Polishchuk ◽  
Z.I. Rossokha ◽  
◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endometrial Cancer ◽  
Hormone Therapy ◽  
Molecular Genetic ◽  
Cancer Syndrome ◽  
Genetic Characteristics ◽  
Multiple Tumors ◽  
Receptor Status ◽  
Genetic Examination ◽  
The Impact

The objective: determining gene polymorphism features ERS1, CYP2D6 in patients with breast cancer (RHZ) and endometrial cancer (EC) and the impact assessment studied genetic characteristics compared to receptor status (immunohistochemical determination of expression levels of ER, PR) tumors and the results of the treatment. Patients and methods. article presents the results of complex clinical, morphological, clinical-genealogical, and molecular-genetic examination of 28 females: 19 patients with breast cancer (BC), 9 patients with endometrial cancer (EC), including 5 patients with primary-multiple tumors (PMT) with and without tumor pathology aggregation in families. Results. The It was determined that in patients’ families malignant tumors of breast, uterine body and/or ovaries prevail that corresponds to Lynch type II syndrome (family cancer syndrome). Molecular-genetic examination of genomic DNA of peripheral blood and histological sections for the presence of SNPs of ESR and CYP2D6*4 genes comparing with the results of immunohistochemical study of tumors for receptors ER and PR status have not found associations between these characteristics; although among EC patients the occurrence of genotypes 397ТТ and 351АА was significantly higher comparing with BC patients (55.55% and 10.5% for genotype 397ТТ,and 15.8% for genotype 351АА, respectively). At the same time the patients with BC and primary-multiple tumors (PMT) of female reproductive system organs (FRSO) that carried mutations in BRCA1 in all the cases demonstrated positive ER and PR receptor status and adverse combinations of polymorphous variants of the genes ESR1 (397СС, 397ТС) and CYP2D6*4 (1846G, 1846GA), suggesting combined effect of these factors on the development of malignant neoplasias of FRSO in families with positive family cancer history. In BC patients, receiving standard hormone therapy with tamoxifen, those, who had genotype 1846GG of the gene CYP2D6*4, in 3 patients (15.8%) of 19 (100%) patients disease recurrence was diagnosed. Conclusion. The obtained results allow clinical use of the assessment of polymorphism frequency of the genes ESR1 and CYP2D6*4 for selection of individual hormone therapy regimens schemes for BC patients, to increase efficacy of dispensary observation after finishing of special therapy for such patients, and also personalization of complex and combined treatment regimens. Key words: breast cancer, endometrial cancer, family cancer syndrome, single nucleotide polymorphisms (SNPs) of the genes ESR1, CYP2D6*4.

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