Associations Between the Purinergic Receptor P2X7 and Leprosy Disease.

Autor:	Souza RDC; Laboratório de Biologia do Reconhecer, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, Brazil., Louvain de Souza T; Faculdade de Medicina de Campos, Campos dos Goytacazes, Brazil.; Núcleo de Diagnóstico e Investigação Molecular, Laboratório de Biotecnologia, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, Brazil., Ferreira CDS; Núcleo de Diagnóstico e Investigação Molecular, Laboratório de Biotecnologia, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, Brazil.; Laboratório de Bioinformática, Laboratório Nacional de Computação Científica, Petrópolis, Brazil., Nascimento LS; Laboratório de Biologia do Reconhecer, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, Brazil., Nahn EP Jr; Faculdade de Medicina de Campos, Campos dos Goytacazes, Brazil., Peixoto-Rangel AL; Laboratório de Biologia do Reconhecer, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, Brazil.
Jazyk:	angličtina
Zdroj:	Frontiers in genetics [Front Genet] 2021 Nov 02; Vol. 12, pp. 730991. Date of Electronic Publication: 2021 Nov 02 (Print Publication: 2021).
DOI:	10.3389/fgene.2021.730991
Abstrakt:	Leprosy is an infectious disease still highly prevalent in Brazil, having been detected around 27,863 new cases in 2019. Exposure to Mycobacterium leprae may not be sufficient to trigger the disease, which seems to be influenced by host immunogenetics to determine resistance or susceptibility. The purinergic receptor P2X7 plays a crucial role in immunity, inflammation, neurological function, bone homeostasis, and neoplasia and is associated with several infectious and non-infectious diseases. Here, we first compare the P2RX7 expression in RNA-seq experiments from 16 leprosy cases and 16 healthy controls to establish the magnitude of allele-specific expression for single-nucleotide polymorphisms of the gene P2RX7 and to determine the level of gene expression in healthy and diseased skin. In addition, we also evaluated the association of two P2RX7 single-nucleotide polymorphisms (c.1513A>C/rs3751143 and c.1068A>G/rs1718119) with leprosy risk. The expression of P2RX7 was found significantly upregulated at macrophage cells from leprosy patients compared with healthy controls, mainly in macrophages from lepromatous patients. Significant risk for leprosy disease was associated with loss function of rs3751143 homozygous mutant CC [CC vs. AA: p = 0.001; odds ratio (OR) = 1.676, 95% CI = 1.251-2.247] but not with heterozygous AC (AC vs. AA: p = 0.001; OR = 1.429, 95% CI = 1.260-1.621). Contrary, the polymorphic A allele from the gain function of rs1718119 was associated with protection for the development of leprosy, as observed in the dominant model (AA + AG × GG p = 0.0028; OR = 0.03516; CI = 0.1801-0.6864). So, our results suggest that the functional P2X7 purinergic receptor may exert a key role in the Mycobacterium death inside macrophages and inflammatory response, which is necessary to control the disease. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Souza, Louvain de Souza, Ferreira, Nascimento, Nahn Jr and Peixoto-Rangel.)
Databáze:	MEDLINE
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