Interferon c and interleukin-12p40 genetic polymorphisms in brazilian patients with paracoccidioidomycosis

Abstract

Paracoccidioidomycosis, caused by the thermal dimorphic fungus Paracoccidioides brasiliensis, is a chronic systemic granulomatous disease, endemic in South America, mainly in Brazil, being the eighth leading cause of death among infectious and parasitic diseases. Paracoccidioidomycosis infection is characterized by a Th1 response with secretion of IFN-c and basal levels of IL-10 and IL-4. In the acute form or juvenile a Th2 profile is predominant, with production of IL-10 and IL-4 and low levels of IFN-c. In chronic or adult, a mixed Th1 and Th2 profile is observed. The IFN-c can be induced by another cytokine, IL-12, and both are important in cellular immune response. In experimental models, IFN-c confers resistance to infection caused by Paracoccidioides brasiliensis and deficiency of IL-12p40 can cause susceptibility to this mycosis. The differential production of these cytokines may be associated with genetic polymorphisms. Objective: To investigate the association between the single nucleotide polymorphisms (SNP) IL-12B 3¢ UTR +1188 A/C and IFNG +874 T/A and the clinical forms of paracoccidioidomycosis. Materials and methods: DNA was obtained from peripheral blood samples from patients with paracoccidioidomycosis and healthy subjects. SNP IL-12B 3¢ UTR +1188 A/C was investigated with PCR-RFLP (PCR-Restriction Fragment Length Polymorphism) and SNP IFNG +874 T/A was investigated with PCR-ARMS (Polymerase Chain Reaction - Amplification Refractory Mutational System). Amplified products were visualized with electrophoresis on agarose gel. Results: In the SNP IFNG +874 T/A, the AA genotype was more frequent in the chronic multifocal and TA genotype in the unifocal. Considering the SNP IL-12B 3¢ UTR +1188 A/C there was a tendency for predominance of AC genotype in patients with chronic form, while the AA genotype was more frequent in acute. Despite this apparent difference among the groups, no statistically significant difference was observed in genotype distribution and alleles A, T and C. Conclusions: In this study there was no association between genetic polymorphisms of IL-12B 3¢ UTR +1188 A/C or IFNG +874 T/A and paracoccidioidomycosis, as well as with different clinical forms.