International Journal of Infectious Diseases 98 (2020) 447–453

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International Journal of Infectious Diseases

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Investigation of genetic susceptibility to Mycobacterium

tuberculosis (VDR and IL10 genes) in a population with a high level
of substructure in the Brazilian Amazon region
C.A. Silvaa, D.C.R.O. Fernandesb,c, A.C.O. Bragaa,c, G.C. Cavalcanteb, V.A. Sorticac,d,
M.H. Hutzd, D.F.V.B. Lealc, M.R. Fernadesc, M.N. Santana-da-Silvab, S.E. Lopes Valentec,
L.F. Pastanac, P.D.C. Pintob,c, G.E. Costac, A. Ribeiro-dos-Santosb,c, S. Santosb,c,
N.P.C. Santosa,b,c,*
a Facultyof Medicine, Federal University of Pará, 1 Augusto Corrêa Street, University City Prof. José Silveira Netto, CEP 66075-970, Belém, PA, Brazil
b Laboratory of Human and Medical Genetics, Federal University of Pará, 1 Augusto Corrêa Street, University City Prof. José Silveira Netto, CEP 66075-970,
Belém, PA, Brazil
c Nucleus of Oncology Research, High Complexity in Oncology Unit, University Hospital João de Barros Barreto, 4487 Dos Mundurucus Street, CEP 66073-000,

Belém, PA, Brazil

d Department of Genetics, Federal University of Rio Grande do Sul, 9500 Bento Gonçalves Avenue, Building 43323M, CEP 91501-970, PO Box 15053, Porto

Alegre, RS, Brazil

A R T I C L E I N F O A B S T R A C T

Article history: Objectives: Tuberculosis (TB) is an infectious and contagious disease that has been very influential in
Received 6 January 2020 human history and presents high rates of mortality. The objective of this study was to investigate the
Received in revised form 23 June 2020 association of VDR, IL10, and SLC11A1 gene polymorphisms with susceptibility to the presence of
Accepted 25 June 2020
Mycobacterium tuberculosis infection.
Methods: A total of 135 patients with confirmed TB and 141 healthy individuals were included in the
Keywords:
analysis. Blood samples were collected for DNA extraction. Genotyping of the polymorphisms in the VDR
Mycobacterium tuberculosis
and IL10 genes was performed by real-time PCR, and genotyping of the polymorphisms in the SLC11A1
Genomic ancestry
Polymorphism
gene by conventional PCR, followed by visualization in polyacrylamide gel. The genomic ancestry was
VDR obtained using an autosomal panel with 48 insertion/deletion ancestry-informative markers.
IL10 Results: Polymorphisms TaqI (TT, p = 0.004), FokI (CC and CC + CT, p = 0.012 and p = 0.003, respectively),
SLC11A1 and BsmI (GG, p = 0.008) in the VDR gene, as well as A-592C (GC + AG, p = 0.001) in the IL10 gene, were
significantly associated with susceptibility to TB In addition, high production of VDR combined with low
production of IL10 showed protection for the TB group (p = 0.035).
Conclusions: The VDR polymorphisms may confer an increased risk and the IL10 haplotype may be a
protection factor for the presence of M. tuberculosis infection in the Brazilian population.
© 2020 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-
nd/4.0/).

1. Introduction According to the World Health Organization (WHO), 10 million

Tuberculosis (TB) is an infectious and contagious disease caused
by Mycobacterium tuberculosis infection. One-fourth of the global
population has a latent TB infection and 5–15% of people infected
with M. tuberculosis bacteria develop the clinical disease.
* Corresponding author at: Núcleo de Pesquisas em Oncologia, Unidade de Alta
Complexidade em Oncologia, Hospital Universitário João de Barros Barreto, Rua dos
Mundurucus, 4487, CEP 66073-000, Belém, PA, Brazil.
E-mail address: npcsantos.ufpa@gmail.com (N.P.C. Santos).
new TB cases and 1.3 million TB deaths among HIV-negative people
were reported in 2017 (WHO, 2019).
TB may be considered a polygenic and multifactorial disease that
results from a complex interaction between the host's genome,
pathogen characteristics, and environmental conditions, including
social and economic factors (Möller et al., 2010). However, the
occurrence of TB at different rates among ethnicities and families
suggests that human genetic variability is an important factor in the
host response to M. tuberculosis infection and in regulating
susceptibility and progression of the disease (Naranbhai, 2016;
Kinnear et al., 2017; Turner et al., 2017; Abel et al., 2018).

https://doi.org/10.1016/j.ijid.2020.06.090
1201-9712/© 2020 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
448 C.A. Silva et al. / International Journal of Infectious Diseases 98 (2020) 447–453