Expression studies of tuberculosis susceptibility genes

Abstract

The activating research interest in the problem of tuberculosis development is due to the increase in cases of drug resistance, coinfection with HIV and hepatitis, and the lack of an effective vaccine. However, the pathogenesis of tuberculosis remains insufficiently studied at present. A significant role is assigned to hereditary factors, as the majority of those infected with Mycobacterium tuberculosis remain resistant to tuberculosis, and only in 5—15% of cases does infection lead to the development of the disease. Despite a long history of research of genetic factors of susceptibility to tuberculosis infection — from the search for monogenic forms of immune dysfunction, associations of individual tuberculosis susceptibility genes, to the analysis of genome-wide associative studies and the assessment of the characteristics of the transcriptional profiles of patients, — the problem of obtaining clinically significant results for the identification and monitoring of risk groups remains particularly acute. The search of differentially expressed genes in groups with different status of the disease (non-infected, latent tuberculosis infection, presymptomatic state, active tuberculosis, recovery from tuberculosis, non-tuberculosis infection) led to identification of a large number of data which is not overlapped in different compared groups, different ethnic groups, in the studies of the whole blood and cellular models. Merging this wealth of data followed by its reanalysis helps to verify and update results. However, there still is a large number of questions concerning our understanding of the functioning of the human organism under the influence of M. tuberculosis. In recent years, new approaches have been used to develop test systems for the diagnosis of various forms of the disease. The review considers up to date results of expression studies of susceptibility to tuberculosis, namely, objects and approaches of research changing over time, forms of the host response to the mycobacteria infection studied, the influence of different factors on the results.

Keywords

• tuberculosis
• genetic susceptibility
• gene expression
• immune response
• prognostic significance
• biomarker