Proje Geliştirme ve
Koordinasyon Birimi

2016-03-07 Kazakhstan: Study of the role of cytokine genes and their regulatory epigenetic factors in the development of asthma and COPD in East Kazakhstan


Study of the Role of Cytokine Genes and Their Regulatory Epigenetic Factors in the Development of Asthma and COPD in East Kazakhstan

Description of the project offered: 
In recent years, worldwide and in Kazakhstan, the number of patients with asthma and chronic obstructive pulmonary disease (COPD) progressively increases. Genetic susceptibility and environmental factors play important role in the development of asthma and COPD. In 80-90% of cases the cause of COPD is tobacco smoking. The base of these diseases is a chronic inflammation of the respiratory tract, which is caused by increased expression of a multiplicity of inflammatory proteins.
An actual problem is the detection of molecular markers that allow to conduct of the differential diagnosis between these diseases in patients older than 40 years. Moreover, of great interest is the study of the role of environmental factors in the development of asthma and COPD. The increase of spreading of asthma and COPD in the last decades, with a large divergence between populations and differences in ethnic and racial groups living in different conditions, is an evidence of a significant contribution of the environmental factors to the development of diseases. It is known that epigenetic modulation, caused by environmental pollution, can alter the regulation of expression of genes that play an important role in the pathogenesis of asthma and COPD.
Patients with asthma have increase of CD4 + T-lymphocytes in the airways, mainly T-helper 2 cells (Th2), with the corresponding production of cytokines. In bronchial biopsies, small airways and lung parenchyma of patients with COPD is detected infiltration by T cells (predominantly Th1 and cytotoxic cells), increased numbers of neutrophils and macrophages. Epigenetic factors including damage of DNA methylation, histone modifications change, specific expression of microRNAs and other changes in chromatin organization may lead to reprogramming of the immune response - the differentiation of naive T cells into effector various lines, especially in Th1- and Th2 cells, disruption of the functioning of the dendritic cells, macrophage activation and damage airway epithelial barrier. These changes may contribute to the formation of asthma and COPD.
Regions with a wide range of natural and man-made pollutant impacts on the environment provide opportunities for epigenetic research. A large number of industrial factories in Kazakhstan have a harmful impact on the environment and human health. One of these regions is Eastern Kazakhstan. There are mining and processing of lead, zinc, copper, uranium and others. There is evidence of exceeded indicators such as nitrogen dioxide, sulfur dioxide, formaldehyde, phenol. The greatest threat for East Kazakhstan from the standpoint of environmental safety are the emission of industrial gases and pollution of soil, including radiation.
In the planned study, markers of exposure to pollutants, polymorphic variants of genes, DNA modification of histone proteins, the expression of specific miRNAs in immune cells will be studied in a healthy population, patients with asthma and COPD. The study will include people who live in disadvantaged environment and human settlements, free from pollution.
Project proposer:   Almira Akparova (Kazakhstan)
Partner role:  Project participant 
Partner organisation:  Education
Call for proposal title:  N/A 

Description of the collaboration sought: 
We are looking for partners with experience and interest in the study of this problem. Partners can come from different spheres: health, academic and research sector.
Required experience and skills of partners: knowledge and experience in molecular biology and genomic studies of diseases, identification of disease patterns (SNPs, microRNA expression, alterations in DNA methylation, histone modification). 
Expertise sought: Life sciences, Medicine. Health, 
Roles sought: Project coordinator, Project participant, 
Organisation types sought: Consultancy, Education, Research, 
Countries sought: Austria, Belgium, Bulgaria, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, United Kingdom, Albania, Bosnia and Herzegovina, Croatia, Iceland, Israel, Liechtenstein, Macedonia, the former Yugoslav Republic of, Montenegro, Norway, Serbia, Switzerland, Turkey, United States, Andorra