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基因启动子区域多态性与球孢子菌病严重程度的关联。

Polymorphism in the Promoter Region of the Gene and the Association With Severity on Paracoccidioidomycosis.

机构信息

Laboratory of Medical Investigation in Immunology (LIM48), Faculdade de Medicina, Hospital das Clínicas, University of São Paulo, São Paulo, Brazil.

Institute of Tropical Medicine, Faculdade de Medicina, University of São Paulo, São Paulo, Brazil.

出版信息

Front Immunol. 2020 Oct 1;11:542210. doi: 10.3389/fimmu.2020.542210. eCollection 2020.

Abstract

Paracoccidioidomycosis (PCM) is an important endemic, systemic disease in Latin America caused by spp. This mycosis has been associated with high morbidity and sequels, and its clinical manifestations depend on the virulence of the infecting strain, the degree and type of immune response, infected tissues, and intrinsic characteristics of the host. The T helper(Th)1 and Th17/Th22 cells are related to resistance and control of infection, and a Th2/Th9 response is associated with disease susceptibility. In this study, we focused on interleukin(IL)-12p35 (), IL-18 (), and IFN-γ receptor 1 () genetic polymorphisms because their respective roles have been described in human PCM. Real-time PCR was employed to analyze -504 G/T (rs2243115), -607 C/A (rs1946518), and -611 A/G (rs1327474) single nucleotide polymorphisms (SNP). One hundred forty-nine patients with the acute form (AF), multifocal chronic (MC), or unifocal chronic (UC) forms of PCM and 110 non-PCM individuals as a control group were included. In the unconditional logistic regression analysis adjusted by ethnicity and sex, we observed a high risk of the -607 -allele for both AF [ = 0.015; OR = 3.10 (95% CI: 1.24-7.77)] and MC groups [ = 0.023; OR = 2.61 (95% CI: 1.14-5.96)] when compared with UC. The -607 -allele associated risk for the AF and MC groups as well as the protective role of the -allele in UC are possibly linked to higher levels of IL-18 at different periods of the course of the disease. Therefore, a novel role of -607 C/A SNP is shown in the present study, highlighting its importance in the outcome of PCM.

摘要

球孢子菌病(PCM)是拉丁美洲一种重要的地方性、系统性疾病,由 引起。这种真菌病与高发病率和后遗症有关,其临床表现取决于感染菌株的毒力、免疫反应的程度和类型、感染组织以及宿主的内在特征。辅助性 T 细胞(Th)1 和 Th17/Th22 细胞与感染的抵抗和控制有关,而 Th2/Th9 反应与疾病易感性有关。在这项研究中,我们专注于白细胞介素(IL)-12p35()、IL-18()和 IFN-γ 受体 1()的遗传多态性,因为它们各自的作用在人类 PCM 中已有描述。采用实时 PCR 分析 -504 G/T(rs2243115)、-607 C/A(rs1946518)和-611 A/G(rs1327474)单核苷酸多态性(SNP)。纳入 149 例急性(AF)、多灶性慢性(MC)或单灶性慢性(UC)PCM 患者和 110 名非 PCM 个体作为对照组。在按种族和性别调整的非条件逻辑回归分析中,我们观察到 -607-等位基因在 AF [=0.015;比值比(OR)=3.10(95%置信区间:1.24-7.77)]和 MC 组 [=0.023;OR=2.61(95%CI:1.14-5.96)]中均存在高风险。-607-等位基因与 AF 和 MC 组相关的风险以及 -等位基因在 UC 中的保护作用可能与疾病过程不同时期 IL-18 水平升高有关。因此,本研究显示-607 C/A SNP 具有新的作用,突出了其在 PCM 结局中的重要性。

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