PMID- 33117339 OWN - NLM STAT- MEDLINE DCOM- 20210428 LR - 20210428 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 11 DP - 2020 TI - Polymorphism in the Promoter Region of the IL18 Gene and the Association With Severity on Paracoccidioidomycosis. PG - 542210 LID - 10.3389/fimmu.2020.542210 [doi] LID - 542210 AB - Paracoccidioidomycosis (PCM) is an important endemic, systemic disease in Latin America caused by Paracoccidioides 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 (IL12A), IL-18 (IL18), and IFN-gamma receptor 1 (IFNGR1) genetic polymorphisms because their respective roles have been described in human PCM. Real-time PCR was employed to analyze IL12A-504 G/T (rs2243115), IL18-607 C/A (rs1946518), and IFNGR1-611 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 IL18-607 A-allele for both AF [p = 0.015; OR = 3.10 (95% CI: 1.24-7.77)] and MC groups [p = 0.023; OR = 2.61 (95% CI: 1.14-5.96)] when compared with UC. The IL18-607 A-allele associated risk for the AF and MC groups as well as the protective role of the C-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 IL18-607 C/A SNP is shown in the present study, highlighting its importance in the outcome of PCM. CI - Copyright (c) 2020 Sato, Busser, Carvalho, Gomes dos Santos, Sadahiro, Diogo, Kono, Moretti, Luiz and Shikanai-Yasuda. FAU - Sato, Paula Keiko AU - Sato PK AD - Laboratory of Medical Investigation in Immunology (LIM48), Faculdade de Medicina, Hospital das Clinicas, University of Sao Paulo, Sao Paulo, Brazil. AD - Institute of Tropical Medicine, Faculdade de Medicina, University of Sao Paulo, Sao Paulo, Brazil. FAU - Busser, Felipe Delatorre AU - Busser FD AD - Laboratory of Medical Investigation in Immunology (LIM48), Faculdade de Medicina, Hospital das Clinicas, University of Sao Paulo, Sao Paulo, Brazil. AD - Institute of Tropical Medicine, Faculdade de Medicina, University of Sao Paulo, Sao Paulo, Brazil. FAU - Carvalho, Flavia Mendes da Cunha AU - Carvalho FMDC AD - Laboratory of Medical Investigation in Immunology (LIM48), Faculdade de Medicina, Hospital das Clinicas, University of Sao Paulo, Sao Paulo, Brazil. AD - Department of Infectious and Parasitic Diseases, Faculdade de Medicina, University of Sao Paulo, Sao Paulo, Brazil. FAU - Gomes Dos Santos, Alexandra AU - Gomes Dos Santos A AD - Laboratory of Medical Investigation in Immunology (LIM48), Faculdade de Medicina, Hospital das Clinicas, University of Sao Paulo, Sao Paulo, Brazil. AD - Department of Infectious and Parasitic Diseases, Faculdade de Medicina, University of Sao Paulo, Sao Paulo, Brazil. FAU - Sadahiro, Aya AU - Sadahiro A AD - Department of Parasitology, Instituto de Ciencias Biologicas, Federal University of Amazonas, Manaus, Brazil. FAU - Diogo, Constancia Lima AU - Diogo CL AD - Laboratory of Medical Investigation in Immunology (LIM48), Faculdade de Medicina, Hospital das Clinicas, University of Sao Paulo, Sao Paulo, Brazil. AD - Institute of Tropical Medicine, Faculdade de Medicina, University of Sao Paulo, Sao Paulo, Brazil. FAU - Kono, Adriana Satie Goncalves AU - Kono ASG AD - Infectious Diseases Division, Hospital das Clinicas, University of Sao Paulo, Sao Paulo, Brazil. FAU - Moretti, Maria Luiza AU - Moretti ML AD - Faculdade de Ciencias Medicas, Hospital das Clinicas, State University of Campinas, Campinas, Brazil. FAU - Luiz, Olinda do Carmo AU - Luiz ODC AD - Department of Preventive Medicine, Faculdade de Medicina, University of Sao Paulo, Sao Paulo, Brazil. FAU - Shikanai-Yasuda, Maria Aparecida AU - Shikanai-Yasuda MA AD - Laboratory of Medical Investigation in Immunology (LIM48), Faculdade de Medicina, Hospital das Clinicas, University of Sao Paulo, Sao Paulo, Brazil. AD - Institute of Tropical Medicine, Faculdade de Medicina, University of Sao Paulo, Sao Paulo, Brazil. AD - Department of Infectious and Parasitic Diseases, Faculdade de Medicina, University of Sao Paulo, Sao Paulo, Brazil. LA - eng PT - Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201001 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (IL18 protein, human) RN - 0 (Interleukin-18) SB - IM MH - Female MH - Humans MH - *Interleukin-18/genetics/immunology MH - Male MH - Middle Aged MH - Paracoccidioides/immunology MH - *Paracoccidioidomycosis/genetics/immunology MH - *Promoter Regions, Genetic MH - *Severity of Illness Index MH - T-Lymphocytes, Helper-Inducer/immunology PMC - PMC7559583 OTO - NOTNLM OT - IFNGR1 OT - IL12A OT - IL18 OT - Paracoccidioides spp. OT - clinical forms of paracoccidioidomycosis OT - paracoccidioidomycosis OT - single nucleotide polymophism EDAT- 2020/10/30 06:00 MHDA- 2021/04/29 06:00 PMCR- 2020/01/01 CRDT- 2020/10/29 05:51 PHST- 2020/03/11 00:00 [received] PHST- 2020/08/21 00:00 [accepted] PHST- 2020/10/29 05:51 [entrez] PHST- 2020/10/30 06:00 [pubmed] PHST- 2021/04/29 06:00 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2020.542210 [doi] PST - epublish SO - Front Immunol. 2020 Oct 1;11:542210. doi: 10.3389/fimmu.2020.542210. eCollection 2020.