Genes de receptores da resposta imune e a hanseníase em uma população alagoana

Abstract

Leprosy is an infectious disease caused by Mycobacterium leprae that affects the skin and peripheral nerves, leading to physical deformities. The low diversity in your genome makes leprosy a great model to study the host genetic influence of the disease. Evidence shows that genes in the innate immune response, mainly TLR1 and NOD2, are important in the outcome and differentiation of clinical forms and, have been associated in Brazilian populations, however, there is no investigation of the role of these genes in Alagoas. The study aimed to evaluate the association of polymorphisms in the genes TLR1 and NOD2 in leprosy and its clinical forms in an alagoana population. We conducted a case-control study, where the cases were constituted by patients from CRIA (Integrated Reference Center of Arapiraca) and, the controls were healthy individuals, blood donors from Hemoal-Arapiraca. We evaluated the rs4833095-TLR1 e rs8057341-NOD2. The individuals’ DNA who accepted to participate in the study was extracted through the salting-out method and genotyped through Real-Time PCR via allelic discrimination using TaqMan probes. We obtained the alleles, genotypes and allele carriers frequencies, that afterward were compared between the groups through logistic regression. We conducted a systematic review to group the results obtained in a meta-analysis about polymorphisms in the TLR1 gene following PRISMA guidelines. All statistical analyses were performed in R studio version 1.4.1717 using the packages “genetics” and “SNPassoc” for the genetic association analysis and “meta” and “metafor” to meta-analysis”. As result of populational recruitment in Alagoas, we achieved 424 individuals, 159 cases, and 265 controls. The frequency of polymorphisms from Alagoas population (controls) was 17% to TT genotype of rs4833095-TLR1 SNP and 11,8% to TT genotype of rs8057341-NOD2 SNP. In the case-control and genetic association with leprosy the estimates of association were the following: rs4833095-TLR1 C allele with OR=0,90 (p=0,63), TC genotype with OR=1,06 (p=0,83) and CC with OR=0,84 (p=0,58); rs8057341-NOD2 T allele with OR=0,97 (p=0,91), CT genotype with OR= 1,10 (p=0,64) and TT with OR=0,84 (p=0,62). The results show that the studied SNPs do not have an association with leprosy in the investigated population, even after correction to sex co-variate. Furthermore, the association analysis with operational classification (MB versus PB) did not result in association even after correction to sex (p=>0,05). In the meta-analysis, carriers of the C allele of the SNP rs5743618-TLR1 showed association with leprosy exhibiting a protector effect OR= 0,57 (p=0,048). When performed the sensitivity analysis and omitting a study, this protector effect was observed in all genetics models to the same SNP, showing OR=0,48 (p=0,010) to the C allele, OR=0,47 (p=0,028) to C carriers and, OR=0,26 (p=0,003) to CC genotype. The results obtained in the meta-analysis indicated a protector association of SNP rs5743618 of the TLR1 gene and leprosy. The findings of this study aggregate information regarding the genetic influence in leprosy a sample from Alagoas, which may be useful to understand the disease development in the region