Polymorphisms on IFNG, IL12B and IL12RB1 genes and paracoccidioidomycosis in the Brazilian population

• Published in: Infection, genetics and evolution genetics and evolution, 2016-09, Vol.43, p.245-251
• Main Authors: Carvalho, F.M.C., Busser, F.D., Freitas, V.L.T., Furucho, C.R., Sadahiro, A., Kono, A.S.G., Criado, P.R., Moretti, M.L., Sato, P.K., Shikanai-Yasuda, M.A.
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions; Acute Disease; Adolescent; Adult; Aged; Alleles; Brazil; Child; Chronic Disease; Cytokines; Female; Gene Expression; Gene Frequency; Genotype; Host-Pathogen Interactions; Humans; IFNG, IL12B; IL12RB1; Interferon-gamma - genetics; Interferon-gamma - immunology; Interleukin-12 Subunit p40 - genetics; Interleukin-12 Subunit p40 - immunology; Male; Middle Aged; Paracoccidioides - growth & development; Paracoccidioidomycosis; Paracoccidioidomycosis - genetics; Paracoccidioidomycosis - immunology; Paracoccidioidomycosis - microbiology; Paracoccidioidomycosis - pathology; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Receptors, Interleukin-12 - genetics; Receptors, Interleukin-12 - immunology; Sex Factors; SNP
• ISSN: 1567-1348; 1567-7257
• DOI: 10.1016/j.meegid.2016.05.025

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. •IL12RB1 SNP was associated with chronic PCM in men.•There was no association between the IFNG and IL12B SNPs and PCM.•The IL12B and IL12RB1 SNPs were studied for the first time in PCM and its clinical forms.