Full project title:
Seeking for immunological susceptibility markers for leprosy. Identification of SNPs in miRNAs binding sites and their role in immune response modulation in leprosy

Project coordination
Universidade Federal de Minas Gerais

Partners
Instituto Lauro de Souza Lima
Universidade Federal do Sergipe
Instituto Oswaldo Cruz - FioCruz Rio

Aim: This project aims to contribute to identification of host genetic risk factors for leprosy susceptibility.

Project summary
Leprosy is a disease caused by the bacteria Mycobacterium leprae. Although there is effective treatment (multidrug therapy), it is not enough to control leprosy dissemination. Leprosy transmission occurs through close contact between an untreated patient and a susceptible person. If we have an early leprosy diagnosis and transmission monitoring, we can have an early treatment, interrupt leprosy transmission between people and also prevent clinical complications of leprosy.
One way to discover the susceptibility of people to leprosy is to understand how some parts of our DNA, inside our cells, work. Scientists know that the immune response to any pathogen is controlled by the DNA and if this control is somehow altered, one can be more susceptible than others to infections such as leprosy.
Those parts of the DNA may be what we call “genetic markers” and it is very important to study these markers present in our DNA in order to allow us to identify people with higher risks to develop leprosy.
Leprosy susceptibility and severity of the disease varies among people according to immune response profile. Several types of genetic factors control host immune response and, consequently, susceptibility to disease. One of these factors are molecules called microRNAs (miRNAs). MiRNAs act by binding in specific sites in the DNA, controlling its function. If there is a variation in its binding region, it may interfere with its function and disrupt some important mechanisms such as the immune response. One important type of variation in the site of miRNA will bind is called Single Nucleotide Polymorphisms (SNPs).
Those SNPs may influence the response from DNA to an infection, such as production of protecting molecules of the immune response. So, variations on the DNA (SNPs) may increase the risk of developing leprosy or even have a protecting role. In this study, we aim to investigate those variations in the DNA (SNPs), specifically in the regions used for miRNAs to bind and control genes of the immune response, even in leprosy patients and healthy people with close contact to them. Then, we will investigate the association of these genetic variations to an increased risk of developing leprosy.
These variants are potentially useful to identify people with a high risk of developing leprosy giving to them an early diagnosis and treatment, if necessary. It is very important to control leprosy dissemination and also to prevent the clinical complications associated with leprosy progression.