Souza Rebeka da Conceição, Louvain de Souza Thaís, Ferreira Cristina Dos Santos, Nascimento Letícia Silva, Nahn Edilbert Pellegrini, Peixoto-Rangel Alba Lucínia
Laboratório de Biologia do Reconhecer, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, Brazil.
Faculdade de Medicina de Campos, Campos dos Goytacazes, Brazil.
Front Genet. 2021 Nov 2;12:730991. doi: 10.3389/fgene.2021.730991. eCollection 2021.
Leprosy is an infectious disease still highly prevalent in Brazil, having been detected around 27,863 new cases in 2019. Exposure to 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 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 and to determine the level of gene expression in healthy and diseased skin. In addition, we also evaluated the association of two single-nucleotide polymorphisms (c.1513A>C/rs3751143 and c.1068A>G/rs1718119) with leprosy risk. The expression of 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: = 0.001; odds ratio (OR) = 1.676, 95% CI = 1.251-2.247] but not with heterozygous AC (AC vs. AA: = 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 = 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 death inside macrophages and inflammatory response, which is necessary to control the disease.
麻风病是一种在巴西仍然高度流行的传染病，2019年报告了约27863例新发病例。接触麻风杆菌可能不足以引发疾病，该病似乎受宿主免疫遗传学影响，从而决定抵抗力或易感性。嘌呤能受体P2X7在免疫、炎症、神经功能、骨稳态和肿瘤形成中起关键作用，并与多种感染性和非感染性疾病相关。在此，我们首先比较16例麻风病患者和16例健康对照的RNA测序实验中P2X7的表达，以确定该基因单核苷酸多态性的等位基因特异性表达程度，并确定健康皮肤和患病皮肤中的基因表达水平。此外，我们还评估了两个P2X7单核苷酸多态性（c.1513A>C/rs3751143和c.1068A>G/rs1718119）与麻风病风险的关联。结果发现，与健康对照相比，麻风病患者巨噬细胞中P2X7的表达显著上调，主要是在瘤型麻风患者的巨噬细胞中。麻风病的显著风险与rs3751143纯合突变CC的功能丧失有关[CC与AA相比：P = 0.001；比值比（OR）= 1.676，95%置信区间（CI）= 1.251 - 2.247]，但与杂合子AC无关（AC与AA相比：P = 0.001；OR = 1.429，95%CI = 1.260 - 1.621）。相反，rs1718119功能获得性的多态性A等位基因与麻风病发展的保护作用相关，如显性模型所示（AA + AG×GG：P = 0.0028；OR = 0.03516；CI = 0.1801 - 0.6864）。因此，我们的结果表明，功能性P2X7嘌呤能受体可能在巨噬细胞内的细胞死亡和炎症反应中起关键作用，这对于控制疾病是必要的。
