Differential distribution in vitamin D receptor gene variants and expression profile in Northeast Brazil influences upon
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Differential distribution in vitamin D receptor gene variants and expression profile in Northeast Brazil influences upon active pulmonary tuberculosis Maria Eduarda de Albuquerque Borborema1,2 · Jorge José de Souza Pereira1,2 · Aline dos Santos Peixoto3 · Sergio Crovella1,2 · Haiana Charifker Schindler3 · Michelle Christiane da Silva Rabello3 · Jaqueline de Azevêdo Silva1,2 Received: 11 May 2020 / Accepted: 28 August 2020 © Springer Nature B.V. 2020
Abstract Tuberculosis is an infectious disease with variable outcomes. This variability is due to host immune capacity in containing the infection process initiated by the Mycobacterium tuberculosis (MTB). Vitamin D is able to modulate a very specific immune response against MTB infection, and its action relies on vitamin D receptor (VDR) binding. Altered VDR forms may compromise vitamin D pathway and proper immune response after MTB infection. Herein we assessed the relationship of five potentially functional polymorphisms from VDR: rs2228570 FokI, rs11568820 Cdx-2, rs2248098, rs1540339 and rs4760648, with tuberculosis susceptibility. The SNP rs4760648 T/T was associated with differential susceptibility to tuberculosis (OR = 2.50, 95%CI = 1.20–5.36, p = 0.01). The SNP rs1540339 presented association to both T allele (OR = 0.55, 95%CI = 0.35–0.88, p = 0.01) and the T/T genotype (OR = 0.404, 95%CI = 0.20 – 0.78, p = 0.005). The FokI T allele was identified as associated to diminished susceptibility (OR = 0.67, 95% CI = 0.45–0.99, p = 0.04) to active TB, as well as T/T genotype (OR = 0.15, 95%CI = 0.04–0.45, p = 9.58 × 10–5). We also performed the expression analyses and observed a down-regulation of VDR in patients (-10.717 FC, p = 8.42e−12), and according to the presence of associated FokI SNP, we observed that the C/T and T/T genotypes presence increases VDR expression (+ 1.25 and + 2.35 FC, p = 0.425 and p = 0.506, respectively). This study shows that vitamin D receptor variants can influence upon pulmonary tuberculosis susceptibility and VDR mRNA levels are decreased in those patients. Keywords Tuberculosis · Vitamin D · Polymorphisms · M. tuberculosis · VDR · Gene expression * Jaqueline de Azevêdo Silva [email protected] Maria Eduarda de Albuquerque Borborema [email protected] Sergio Crovella [email protected] Haiana Charifker Schindler [email protected] Michelle Christiane da Silva Rabello [email protected] 1
Department of Genetics, Federal University of Pernambuco, Recife, Pernambuco, Brazil
2
Laboratory of Immunopathology Keizo Asami (LIKA), Federal University of Pernambuco, Av. Prof. Moraes Rego, 1235, Recife, Pernambuco CEP 50760‑901, Brazil
3
Oswaldo Cruz Foundation, Aggeu Magalhães Research Centre (FIOCRUZ/CPqAM), Federal University of Pernambuco, Recife, Pernambuco, Brazil
Introduction Tuberculosis (TB) burdens the role of one of the most ancient, compromising and deadly infectious disease worldwide, caused by the Mycobacterium tuberculosis, displays quite variable clinical
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