Banca de DEFESA: JUAN MANUEL CUBILLOS ANGULO

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : JUAN MANUEL CUBILLOS ANGULO
DATE: 23/02/2022
TIME: 13:00
LOCAL: IGM Sala Virtual 5
TITLE:

IMMUNOGENETIC DETERMINANTS FOR TUBERCULOSIS

KEY WORDS:

Mycobacterium tuberculosis; Single nucleotide polymorphism; Tuberculin skin test; CD14; NOD2; Toll-like receptor; Tumor necrosis factor.

PAGES: 96
BIG AREA: Ciências Biológicas
AREA: Genética
SUMMARY:

ABSTRACT Mycobacterium tuberculosis (Mtb) infection affects approximately a quarter of the global population. Host genetic polymorphisms may be important in determining susceptibility to Mtb infection, but their role is not fully understood. In a first study, different SNPs were tested as risk factors for tuberculin skin test (TST)conversion and development of Tuberculosis (TB): TLR2 (rs5743708), TLR4 (rs4986791), TNFA (rs361525), IFNG (rs2430561), IL1B (rs1143627). In a second study, seven additional SNPs were tested for association with TT positivity: candidate genes IFI16-PYHIN1-AIM2 (rs1101998, rs1633256, rs866484), IFIT5 (rs59633641, rs10887959), IFIT1 (rs304478, rs730449.8), and IRF7 (rs11246213). Both studies were conducted on contacts of microbiologically confirmed pulmonary TB cases in reference laboratories. Finally, we performed a systematic review to assess the association between CD14 and NOD2 reported polymorphisms and Mtb diseases, and how this association might differ in distinct ethnic populations. In the prospective study, among the 526 participants, 60 had a conversion to TT, and 44 developed active TB during follow-up. Multivariate regression analysis demonstrated that SNPs in TLR4 genes (odds ratio [OR]: 62, 8, 95% confidence interval [95% CI: 7.5–525.3) and TNFA (OR: 4.2, 95% CI: 1.9– 9.5) were independently associated with TT conversion. In the retrospective studio outside 482 contacts were examined, of which 296 contacts had positive TT. In a multivariate model, we observed in the recessive model that PYHIN1-IFI16-AIM2 rs1101998 (adjusted OR [aOR] = 2.90; 95% CI = 1.24-6.78; p = 0.014) and rs1633256 (aOR = 10, 1; 95% CI = 2.20-46.28; p = 0.003) were associated with an increased risk of TT positivity. In the systematic review, thirteen studies met the selection criteria. Of these, nine investigated CD14 SNPs and six reported a significant association between the T allele and the TT genotypes of SNP rs2569190 and increased risk of Mtb disease. In addition, four studies reported data finding the relationship between NOD2 SNPs and Mtb disease risk, with two reporting significant associations of rs1861759 and rs7194886 and increased risk of Mtb disease in a Han Chinese population. The results suggest associations between immunityrelated genes polymorphisms and the probabilities of Mtb infection. This study contributes to the understanding of associations between immunity-related genes polymorphisms and the probabilities of Mtb infection

BANKING MEMBERS:
Externo à Instituição - MARCELO CORDEIRO DOS SANTOS
Externo à Instituição - JOSÉ ROBERTO LAPA E SILVA - UFRJ
Externo à Instituição - AFRANIO LINEU KRITSKI - UFRJ
Interno - 2236977 - ANTONIO RICARDO KHOURI CUNHA
Presidente - 803.442.755-15 - BRUNO DE BEZERRIL ANDRADE - UFBA