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

Author(s):  
Ye. Stepanova ◽  
◽  
I. Kolpakov ◽  
V. Vdovenko ◽  
V. Zigalo ◽  
...  

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.

Author(s):  
Ye. Stepanova ◽  
◽  
I. Kolpakov ◽  
V. Vdovenko ◽  
V. Zigalo ◽  
...  

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.


Author(s):  
Olga S. Vasilyeva ◽  
Lyudmila P. Kuzmina ◽  
Maria M. Kolyaskina

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.


2011 ◽  
Vol 31 (5) ◽  
pp. 311-316 ◽  
Author(s):  
Abdel Halim Salem ◽  
Alaeddin Yaqoob ◽  
Muhalab Ali ◽  
Shailandra Handu ◽  
Raouf Fadel ◽  
...  

Deletion polymorphisms for the glutathione S-transferase (GST) gene are associated with increased risk of cancer, and are implicated in detoxifying mutagenic electrophilic compounds. GST Polymorphic variants were reported for different populations. The aim of this study was to investigate the frequencies ofGSTM1andGSTT1null genotypes among Bahraini, Lebanese and Tunisian Arabs. GST genotyping was done by multiplex PCR-based methods. Study subjects comprised 167 Bahrainis, 141 Lebanese and 186 Tunisians unrelated healthy individuals.GSTM1deletion homozygosity of 49.7%, 52.5% and 63.4% were recorded for Bahraini, Lebanese and Tunisians, respectively. Among Bahrainis, the prevalence ofGSTT1null homozygotes was 28.7%, while in higher rates were seen in Lebanese (37.6%) and Tunisians (37.1%). Our results indicate that there are no major differences in allelic distribution ofGSTM1and GSTT1 genes between the three Arab populations investigated except between Bahrainis and Tunisians regarding the allelic distribution ofGSTM1gene (P= 0.013). Combined analysis of both genes revealed that 14.4% of Bahrainis, 16.3% of Lebanese and 21.0% of Tunisians harbor the deleted genotype of both genes. This is the first study that addressesGSTgene polymorphism in Bahraini and Lebanese Arabs, and will help genetic studies on the association ofGSTM1andGSTT1polymorphisms with disease risks and drug effects in Arab populations.


1999 ◽  
pp. 123
Author(s):  
Dilek Aktas ◽  
Ali Tekin ◽  
Haluk Ozen ◽  
Necmettin Atsu ◽  
Hawa Simsek ◽  
...  

2011 ◽  
Vol 21 (6) ◽  
pp. 1197-1201
Author(s):  
Asmaa Ahemed Abd El-Aal ◽  
Mostafa M. El-Nashar ◽  
Amal H. El-Sissy

2007 ◽  
pp. 52-55
Author(s):  
I. V. Petrova ◽  
D. V. Kozyritskaya ◽  
E. M. Kamaltynova ◽  
L. M. Ogorodova

The purpose of this work was to study NO-synthase gene polymorphic variants in term of asthma occurrence. Clinical and functional characteristics of asthma with regards to different NO-synthase gene polymorphic variants were analyzed in 250 asthmatic children aged 7 to 14 years under the 12-wk standard basic therapy for asthma. We used the typical spectrum of tests for children with asthma and molecular genetic methods. Polymorphism at the promotor region of the NO-synthase gene was found to be associated with phenotype of pathogenic features of asthma and was an important part of inherited predisposition to asthma.


Sign in / Sign up

Export Citation Format

Share Document