Estudo de associação entre o gene MBL2 e a hanseníase na população de Alagoas, Brasil

Abstract

Leprosy, a chronic infectious disease, is identified as a serious public health problem, as it is still considered the infectious disease that causes the largest number of physical deformities in the world. The etiological agent of the disease is the bacillus Mycobacterium leprae, and the recently associated bacillus, Mycobacterium lepromatosis. These microorganisms are able to overcome a succession of physical barriers until reaching the Schwann cell. Some studies have shown, in different populations, the importance of SNPs in genes associated with leprosy. In this sense, studies that evaluated mutations in the MBL2 gene have received attention. Genetic studies of SNPs of the MBL2 gene have already been associated with leprosy in Brazilian populations, however, there is no investigation into the role of this gene in Alagoas. The aim of the present study was to investigate the association of SNPs rs1800450 and rs1800451 in the MBL2 gene with leprosy in the population of Alagoas, Brazil. A case-control study was conducted, where the cases included patients diagnosed with leprosy at reference centers in the cities of Maceió, Arapiraca, Santana do Ipanema and Penedo, and the controls included healthy individuals, blood donors at HEMOAL-Arapiraca. The DNA of individuals who agreed to participate in the study was extracted using the salting out method and genotyped using real time PCR using allelic discrimination using TaqMan probes. The allele, genotypic and allele carrier frequencies were obtained, which were later compared between the groups using logistic regression. All statistical analyzes were carried out using the R environment (version 1.4.1717). As a result of population recruitment in Alagoas, we obtained 592 individuals, of which 328 were cases and 264 were controls. For the rs1800450 polymorphism in the MBL2 gene, a frequency of 89% was observed in the total population for the C allele, with a frequency of 91% in the group of cases and 86% in controls, being identified as the present polymorphic allele study. In relation to the genotype, CC presented a higher frequency in both cases (84%) and controls (72%), suggesting the distribution of genotypes of this SNP in the Alagoas population. For the rs1800451 polymorphism in the MBL2 gene, a frequency of 93% in the total population was observed for the C allele, with the same percentage in both the case and control groups. While the T allele presented a frequency of only 7% in the total population, it also had the same frequency in the case and control groups. In relation to the genotype, CC was more frequent in both cases (86%) and controls (87%), the lowest frequency genotype found was TT with 1% in cases and none in controls, and the heterozygous CT in cases was 12% and 13% in controls. In the genotypic association analysis, we can observe that there was an association between the CT genotype of the SNP rs1800450 of the MBL2 gene and the leprosy protection factor both before (p: 0.0007, OR: 0.49, CI: 0.32-0.74 ) as well as after adjusting for sex in the logistic regression (p: 0.001, OR: 0.51, CI: 0.33-0.77). The frequencies of T allele carriers were also obtained, and a positive result of association of the SNP rs1800450 of the MBL2 gene for protection against leprosy was observed, both before (p: 0.001, OR: 0.50, CI: 0.34-0 .76) and how much after adjustment for the covariate sex (p: 0.002, OR: 0.52, CI: 0.35-0.79). As for the SNP rs1800451, there was no association of the T allele with leprosy (p: 0.71, OR: 1.13, CI: 0.59 – 2.16), the same is visualized when including the variable sex (p: 0 .73, OR: 1.12, IC: 0.58 – 2.15). There continues to be no association when analyzing the genotypes and T carriers, both before and after inclusion of the sex variable. The findings of the present study add information regarding the genetic influence on leprosy in a population of Alagoas, which may be useful for understanding the development of the disease in the region, in addition, it may identify high-risk individuals prone to prophylactic measures, such as treatment with single dose rifampin and BCG vaccination.