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

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

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.542210

DOI=10.3389/fimmu.2020.542210

ISSN=1664-3224

ABSTRACT=<p>Paracoccidioidomycosis (PCM) is an important endemic, systemic disease in Latin America caused by <italic>Paracoccidioides</italic> 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 (<italic>IL12A</italic>), IL-18 (<italic>IL18</italic>), and IFN-γ receptor 1 (<italic>IFNGR1</italic>) genetic polymorphisms because their respective roles have been described in human PCM. Real-time PCR was employed to analyze <italic>IL12A</italic>-504 G/T (rs2243115), <italic>IL18</italic>-607 C/A (rs1946518), and <italic>IFNGR1</italic>-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 <italic>IL18</italic>-607 <italic>A</italic>-allele for both AF [<italic>p</italic> = 0.015; OR = 3.10 (95% CI: 1.24–7.77)] and MC groups [<italic>p</italic> = 0.023; OR = 2.61 (95% CI: 1.14–5.96)] when compared with UC. The <italic>IL18</italic>-607 <italic>A</italic>-allele associated risk for the AF and MC groups as well as the protective role of the <italic>C</italic>-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 <italic>IL18</italic>-607 C/A SNP is shown in the present study, highlighting its importance in the outcome of PCM.</p>