Banca de QUALIFICAÇÃO: HELOISA DE ALMEIDA FREITAS

Investigation of genetic polymorphism at immune response molecules in susceptibility to leprosy development in a sample from Alagoas, Brazil

Human and medical genetics; SNPs; Immunology; Cytokines; Case-control 

Leprosy is a disease caused mainly by the obligate intracellular bacillus Mycobacterium leprae, and Mycobacterium lepromatosis, which mainly affects the skin and peripheral nerves, which can result in physical disabilities. The state of Alagoas, in 2022, presented an incidence rate of new cases of 9.67/100 thousand inhabitants (average endemicity), with several municipalities showing hyperendemicity. The interactions between pathogen characterization, host genetics and operating environment are factors to be considered for the development of leprosy. Among the host's genetics, there are immune response genes, and in them, there are SNPs that are equal to or greater than 1% of a given population and are risk or protective factors for leprosy. Among the immune response genes, we have the CCDC122-LACC1 gene which is one of the regulators of the metabolic function of macrophages, the IL23R which plays an important role in immune regulation, and the RAB32 responsible for regulating the clearance of aggregated proteins by autophagy. To understand the genetic basis of leprosy, the SNPs rs4942254/CCDC122-LACC1, rs3762318/IL23R and rs2144658/IL23R were investigated, and rs2275606/RAB32, which have already been investigated in Brazilian and Chinese populations, but their influence on the population has not yet been verified alagoana. The objective was to investigate the association of SNPs belonging to the IL23R, CCDC122-LACC1 and RAB32 genes with leprosy in a population sample from Alagoas. A case-control study was carried out, using samples of individuals with leprosy (cases) and without leprosy (controls), recruited in Alagoas. After collecting biological samples and extracting DNA (salting out), genotyping of the SNPs rs2144658/IL23R and rs3762318/IL23R, rs4942254/CCDC122-LACC1 and rs2275606/RAB32 was performed using real-time PCR (Taqman assay, StepOne Plus^TM). Statistical analyzes used OR, CI and p values as a measure of association, and were carried out in the R environment (version 4.3.0) using the “genetics” and “SNPassoc” packages. As a result, 287 cases and 264 controls were included in the genetic study. So far, the results have revealed that the rs3762318 and rs2144658 polymorphisms, both in the IL23R gene, are not associated with leprosy in the population investigated, even after adjustment with the covariate sex (OR_AG: 1.04, p-value: 0.84; OR_AG: 0.87, p-value: 0.58, respectively). As for the frequencies of the CC homozygote of the rs4942254/CCDC122-LACC1 polymorphism, they were 15% for cases and 22% for controls. The results demonstrated that the SNP investigated in the CCDC122-LACC1 gene was associated with protection against leprosy in the Alagoas population (OR_CC= 0.51, p= 0.016). The results obtained so far have identified the SNP rs4942254 in the CCDC122-LACC1 gene associated with a lower risk of leprosy, contributing to information regarding the genetic influence of the disease in the population of Alagoas.