Banca de QUALIFICAÇÃO: LUANA KAREN CORREIA DOS SANTOS

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : LUANA KAREN CORREIA DOS SANTOS
DATE: 11/03/2021
TIME: 15:00
LOCAL: Vídeo-conferência
TITLE:

Immune Response Receptors Genes and Leprosy in an Alagoana Population

KEY WORDS:

Genetics. Immunology. Mycobacterium leprae.

PAGES: 93
BIG AREA: Ciências Biológicas
AREA: Genética
SUMMARY:

Leprosy is an infectious disease caused by Mycobacterium leprae that affects the skin and peripheral nerves, leading to physical deformities. It is considered a complex disease that suffers the influence of many factors, furthermore, 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 at CRIA (Integrated Reference Center of Arapiraca) and, the controls were healthy individuals, blood donors at Hemoal-Arapiraca. We evaluated the rs4833095 and rs8057341 in the genes TLR1 and NOD2, respectively. The individuals’ DNA who accepted to participate in the study was extracted through the salting-out method and genotyped through Real-Time qPCR via allelic discrimination (Applied Biosystems) using TaqMan probes. We obtained the 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 Moose guidelines. All statistical analyses were performed in R studio version 1.4.1103 using the packages “genetics” and “SNPassoc” for the genetic association analysis and “meta” and “metafor” to meta-analysis”. As result, we achieved 399 recruited individuals, 134 cases, and 265 controls. The frequency of polymorphisms in the alagoana population (controls) was 18% to TT genotype of rs4833095-TLR1 SNP and 12% 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 TC genotype with OR=0,87 (p=0,71) and CC with OR=1,0 (p=0,98); rs8057341-NOD2 CT genotype with OR= 0,92 (p=0,78) and TT with OR=1,03 (p=0,93). 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. In the meta-analysis, only carriers of the C allele of the SNP rs5743618-TLR1 showed association with leprosy OR= 0,57 (p=0,048) exhibited a protector effect. 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 indicate 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 in Alagoas, which may be useful to understand the disease development in the region.

BANKING MEMBERS:
Presidente - 2269479 - CAROLINNE DE SALES MARQUES
Externa à Instituição - ALINE CRISTINE PEREIRA E SILVA - NENHUMA
Externa à Instituição - LUCIA ELENA ALVARADO ARNEZ