title: Polymorphisms on IFNG, IL12B and IL12RB1 genes and paracoccidioidomycosis in the Brazilian population.
abstract: Paracoccidioidomycosis (PCM) is a systemic chronic mycosis, endemic in Latin America, especially Brazil, and is the eighth leading cause of death among chronic and recurrent infectious diseases. PCM infection is characterized by the presence of Th1 immune response; the acute form, by a mixed Th2/Th9, while the chronic form is characterized by Th17/Th22 profiles. The occurrence and severity of human PCM may also be associated with genetic factors such as single nucleotide polymorphisms (SNP) on cytokines encoding genes. We investigated the association between these polymorphisms and the different clinical forms of PCM. We included 156 patients with PCM (40 with the acute form, 99 with the chronic multifocal and 17 with the chronic unifocal form) and assayed their DNA samples for IFNG +874 T/A SNP by PCR-ARMS (Amplification Refractory Mutational System), IL12B +1188 A/C SNP on 3' UTR and IL12RB1 641 A/G SNP on exon 7 by PCR-RFLP (Restriction Fragment Length Polymorphism). We found similar genotypic and allelic frequencies of the investigated SNPs among the clinical forms of PCM. Considering male patients, the IL12RB1 641 AA genotype was more frequent in the chronic multifocal form while heterozygosis was in the chronic unifocal form of PCM (p=0.048). Although our data suggest that the AA genotype (IL12RB1) may be associated with the more disseminated chronic disease, more patients of the chronic unifocal PCM group need to be analyzed as well as the secretion patterns of IFN-γ combined with the IL-12Rβ1 expression for a better comprehension of this association.
authors.affiliation: Department of Infectious and Parasitic Diseases, Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 470 (IMT1, 1°. andar), 05403-000 São Paulo, SP, Brazil; Laboratory of Medical Investigation in Immunology (LIM-48), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 470 (IMT2, térreo, sala 12), 05403-000 São Paulo, SP, Brazil. Electronic address: flavinhamch@gmail.com.
authors.forename: F M C
authors.initials: FM
authors.lastname: Carvalho
authors.affiliation: Laboratory of Medical Investigation in Immunology (LIM-48), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 470 (IMT2, térreo, sala 12), 05403-000 São Paulo, SP, Brazil. Electronic address: felipe_db89@hotmail.com.
authors.forename: F D
authors.initials: FD
authors.lastname: Busser
authors.affiliation: Laboratory of Medical Investigation in Immunology (LIM-48), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 470 (IMT2, térreo, sala 12), 05403-000 São Paulo, SP, Brazil. Electronic address: vera_lucia@yahoo.com.
authors.forename: V L T
authors.initials: VL
authors.lastname: Freitas
authors.affiliation: Laboratory of Medical Investigation in Immunology (LIM-48), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 470 (IMT2, térreo, sala 12), 05403-000 São Paulo, SP, Brazil. Electronic address: celiarf@usp.br.
authors.forename: C R
authors.initials: CR
authors.lastname: Furucho
authors.affiliation: Department of Parasitology, Instituto de Ciências Biológicas, Universidade Federal do Amazonas, Av. General Rodrigo Octávio, 6200, Coroado 69077-000, Amazonas, Brazil. Electronic address: asadahiro@ufam.edu.br.
authors.forename: A
authors.initials: A
authors.lastname: Sadahiro
authors.affiliation: Infectious Diseases Division, Hospital das Clínicas, Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 155 (5°. andar, Bloco 2A), 05403-000 São Paulo, SP, Brazil. Electronic address: adriana.kono@uol.com.br.
authors.forename: A S G
authors.initials: AS
authors.lastname: Kono
authors.affiliation: Dermatological Clinic Division, Hospital das Clínicas, Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 255 (5°. andar, Bloco 2B), 05403-000 São Paulo, SP, Brazil. Electronic address: prcriado@usp.br.
authors.forename: P R
authors.initials: PR
authors.lastname: Criado
authors.affiliation: Hospital das Clínicas, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Rua Vital Brasil, 251, Cidade Universitária, 13083-888, Campinas, SP, São Paulo, Brazil. Electronic address: moretti@hc.unicamp.br.
authors.forename: M L
authors.initials: ML
authors.lastname: Moretti
authors.affiliation: Department of Infectious and Parasitic Diseases, Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 470 (IMT1, 1°. andar), 05403-000 São Paulo, SP, Brazil; Laboratory of Medical Investigation in Immunology (LIM-48), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 470 (IMT2, térreo, sala 12), 05403-000 São Paulo, SP, Brazil. Electronic address: paulaksato@yahoo.com.
authors.forename: P K
authors.initials: PK
authors.lastname: Sato
authors.affiliation: Department of Infectious and Parasitic Diseases, Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 470 (IMT1, 1°. andar), 05403-000 São Paulo, SP, Brazil; Laboratory of Medical Investigation in Immunology (LIM-48), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 470 (IMT2, térreo, sala 12), 05403-000 São Paulo, SP, Brazil. Electronic address: maria.shikanai@hc.fm.usp.br.
authors.forename: M A
authors.initials: MA
authors.lastname: Shikanai-Yasuda
mesh_terms: D020413:3' Untranslated Regions; D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001938:Brazil; D002648:Child; D002908:Chronic Disease; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D005838:Genotype; D054884:Host-Pathogen Interactions; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics* / Q000276:immunology; D053762:Interleukin-12 Subunit p40 / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010228:Paracoccidioides / Q000254:growth & development; D010229:Paracoccidioidomycosis / Q000235:genetics* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D053707:Receptors, Interleukin-12 / Q000235:genetics* / Q000276:immunology; D012737:Sex Factors
chemical_list: D020413:3' Untranslated Regions; C573415:IFNG protein, human; C500879:IL12B protein, human; C508438:IL12RB1 protein, human; D053762:Interleukin-12 Subunit p40; D053707:Receptors, Interleukin-12; D007371:Interferon-gamma
keywords: Cytokines; IFNG, IL12B; IL12RB1; Paracoccidioidomycosis; SNP