Banca de DEFESA: HELOISA DE ALMEIDA FREITAS

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : HELOISA DE ALMEIDA FREITAS
DATE: 22/02/2024
TIME: 10:00
LOCAL: Sala 19 do ICBS
TITLE:

GENETIC POLYMORPHISMS IN IMMUNE RESPONSE MOLECULES IN LEPROSY IN A POPULATION IN NORTHEAST BRAZIL

KEY WORDS:

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

PAGES: 107
BIG AREA: Ciências Biológicas
AREA: Genética
SUBÁREA: Genética Humana e Médica
SUMMARY:

Leprosy is a disease caused by the obligate intracellular bacillus
Mycobacterium leprae, and Mycobacterium lepromatosis, which mainly
affects the skin and peripheral nerves. 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 the characterization of the pathogen, the genetics
of the host and the 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 single or simple nucleotide
polymorphisms (SNPs) that are present equal to or greater than 1% of a
given population and are risk or protective factors against leprosy. Among the
immune response genes, there is the IL23R gene, which plays an important
role in immune regulation, CCDC122-LACC1, which is one of the regulators
of the metabolic function of macrophages, and 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. from Alagoas. 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 PlusTM).
Statistical analyzes used OR (Odds Ratio), CI (Confidence Interval) 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, 313 cases and 264 controls were included in the genetic study.
To date, the results have demonstrated that the rs3762318 and rs2144658
polymorphisms, both in the IL23R gene, are not associated with leprosy in the
population investigated, even after adjusting for the covariate sex (ORAG:
1.04, p-value: 0.84; ORAG: 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 (ORCC:
0.51, p: 0.016). As for the SNP rs2275606, an association with the risk of
leprosy was identified in the population of Alagoas (ORAA: 3.12, p: 0.0028,
adjusted). Therefore, it was possible to identify that the SNP
rs4942254/CCDC122-LACC1 was associated with a lower risk of leprosy,
while rs2275606/RAB32 was associated with a higher risk of leprosy. These

findings integrated the panel of markers and their genetic influence on leprosy
in the Alagoas population.

COMMITTEE MEMBERS:
Externo(a) ao Programa - 2361727 - CARLOS ALBERTO DE CARVALHO FRAGA - nullPresidente - 1867374 - ELAINE VIRGINIA MARTINS DE SOUZA FIGUEIREDO
Interno(a) - 1298235 - EMILIANO DE OLIVEIRA BARRETO