Differential distribution in vitamin D receptor gene variants and expression profile in Northeast Brazil influences upon active pulmonary tuberculosis.
Mol Biol Rep
; 47(9): 7317-7322, 2020 Sep.
Article
en En
| MEDLINE
| ID: mdl-32880832
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tuberculosis Pulmonar
/
Receptores de Calcitriol
/
Predisposición Genética a la Enfermedad
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Polimorfismo de Nucleótido Simple
/
Mycobacterium tuberculosis
Tipo de estudio:
Prognostic_studies
Límite:
Female
/
Humans
/
Male
/
Middle aged
País/Región como asunto:
America do sul
/
Brasil
Idioma:
En
Revista:
Mol Biol Rep
Año:
2020
Tipo del documento:
Article
País de afiliación:
Brasil
Pais de publicación:
Países Bajos