Estudo de associação entre os genes IL10, IL6 e APOE e a hanseníase em uma população do agreste de Alagoas

Abstract

Leprosy is a chronic infectious disease caused by the bacterium Mycobcterium leprae and mainly affects the skin and peripheral nerves. Brazil is the second country in the world in number of leprosy cases. In the period from 2014 to 2019, about 164,000 new cases of leprosy were reported in the country. In the state of Alagoas in 2019, the incidence rate of the disease was 6.95/100 thousand inhabitants, being considered highly endemic. Thus, the importance of investigating the possible risk factors related to the occurrence of the disease in the region of Alagoas is highlighted. One of the factors related to the development of leprosy is the genetic component of the host, especially Single Nucleotide Polymorphism (SNP) in genes related to cytokines of the immune response in the pathophysiology of the disease. Studies already carried out in other populations showed an association of polymorphisms in the cytokine genes IL10, IL6 and APOE. Thus, the aim of the present study was to investigate associations of SNPs in the IL10, IL6 and APOE genes with leprosy and its clinical and operational forms. A casecontrol study was carried out including patients with leprosy diagnosed at the Centro de Referência Integrado de Arapiraca (CRIA). To compose the control group, volunteers with no history of infectious diseases were recruited at the Blood Center of Arapiraca-AL (HEMOAL). After that, biological samples were collected (peripheral whole blood) from which DNA extraction was performed by the salting-out method (or DNA precipitation method). From the extracted DNA, the genotyping of SNPs in these genes was performed, using allelic discrimination assays by Polymerase Chain Reaction (PCR) in real time. The analyzes were performed using the logistic regression model, which also allows the inclusion of possible covariables that may introduce some type of bias in the analyses, generating measures of genetic association with leprosy. All analyzes were performed in R environment, version (2021-05-18), with the aid of R studio software. As a result of population recruitment in the rural region of Alagoas, 445 individuals were recruited, being 181 cases (15.8% PB and 66.2% MB) and 264 controls. The frequency of polymorphisms in the population of Alagoas (controls) was 48% for CT genotype for SNP rs1800871-IL10, 48% for AG genotype for SNP rs2069845-IL6 and 48% for GT genotype for SNP rs405509-APOE . The analysis of genetic association with leprosy resulted in the following estimates: OR=1.75 (p=0.08) for the TT genotype of SNP rs1800871- IL10, OR=1.31 (p=0.36) for the GG of the rs2069845-IL6 SNP and OR=1.13 (p=0.67) for the TT of the rs405509-APOE SNP. The results demonstrate that the SNPs studied are not associated with leprosy per se in the population studied, even after correction for the covariate sex. The analysis according to the operational classification showed an association of SNP rs2069845-IL6 with an increased risk for MB leprosy compared to PB, which remained even after correction for sex (genotype GG, OR= 2.91; p=0, 03). The results obtained in the present study, contribute to the information about the genetic influence on leprosy in a population of Alagoas, and can later be used to compose a panel of markers for the disease, mainly for clinical severity, making it possible to monitor patients and verify the chances of developing the most severe form of leprosy.