Journal Article

Polymorphism in the Promoter Region of the IL18 Gene and the Association With Severity on Paracoccidioidomycosis

Busser, Felipe Delatorre, Kono, Adriana Satie Gonçalves, Gomes dos Santos, Alexandra, Sadahiro, Aya, Diogo, Constancia Lima, Moretti, Maria Luiza, Shikanai-Yasuda, Maria Aparecida, Luiz, Olinda do Carmo, Sato, Paula Keiko, Carvalho, Flávia Mendes da Cunha

2020

Overview

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.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Alleles / Antibodies / Chronic illnesses / Cytokines / Female / Fungal infections / Gene polymorphism / Genes / Genotype & phenotype / Helper cells / Humans / IFNGR1 / IL12A / IL18 / Immune response / Immunity (Disease) / Immunology / Infectious diseases / Interleukin 18 / Interleukin-18 - genetics / Interleukin-18 - immunology / Lymphocytes T / Male / Middle Aged / Morbidity / Mutation / Mycosis / Paracoccidioides - immunology / Paracoccidioides spp / paracoccidioidomycosis / Paracoccidioidomycosis - genetics / Paracoccidioidomycosis - immunology / Polymorphism / Promoter Regions, Genetic / Severity of Illness Index / single nucleotide polymophism / Single-nucleotide polymorphism / South American blastomycosis / T-Lymphocytes, Helper-Inducer - immunology / Tropical diseases / Tuberculosis / Virulence / γ-Interferon