RESUMEN
INTRODUCTION: A single nucleotide polymorphism (SNP) in the gene encoding gamma interferon influences its production and is associated with severity of infectious diseases. This study aimed to evaluate the association of IFNγ+874T/A SNP with duration of disease, morbidity, and development of retinochoroiditis in acute toxoplasmosis. METHODS: A case-control study was conducted among 30 patients and 90 controls. RESULTS: Although statistical associations were not confirmed, A-allele was more common among retinochoroiditis cases and prolonged illness, while T-allele was more frequent in severe disease. CONCLUSIONS: Despite few cases, the results could indicate a relation between IFNγ+874T/A single nucleotide polymorphism and clinical manifestations of toxoplasmosis.
INTRODUÇÃO: Um polimorfismo de nucleotideo único (SNP) no gene codificante para interferon gama influencia a sua produção e pode estar associado à gravidade de diversas doenças infecciosas. O objetivo deste estudo foi avaliar a associação entre SNP para IFNγ+874T/A com a duração da doença, a morbidade e o desenvolvimento de retinocoroidite na toxoplasmose aguda. MÉTODOS: Estudo de caso-controle incluindo 30 pacientes e 90 controles. RESULTADOS: Apesar da ausência de associação estatística, o alelo A foi mais comum entre os casos com retinocoroidite e doença prolongada e o alelo T nas formas mais severas. CONCLUSÕES: Os dados encontrados sugerem uma relação entre o polimorfismo de base única em IFNγ+874T/A com a morbidade e com o desenvolvimento de retinocoroidite por toxoplasmose.
Asunto(s)
Adulto , Femenino , Humanos , Masculino , Coriorretinitis/parasitología , Frecuencia de los Genes , Interferón gamma/genética , Polimorfismo de Nucleótido Simple/genética , Toxoplasmosis/genética , Enfermedad Aguda , Estudios de Casos y Controles , Coriorretinitis/genética , Predisposición Genética a la Enfermedad , Genotipo , Índice de Severidad de la Enfermedad , Toxoplasmosis Ocular/genéticaRESUMEN
Toxoplasma gondii infection is an important mediator of ocular disease in Brazil more frequently than reported from elsewhere. Infection and pathology are characterized by a strong proinflammatory response which in mice is triggered by interaction of the parasite with the toll-like receptor (TLR)/MyD88 pathway. A powerful way to identify the role of TLRs in humans is to determine whether polymorphisms at these loci influence susceptibility to T. gondii-mediated pathologies. Here we report on a small family-based study (60 families; 68 affected offspring) undertaken in Brazil which was powered for large effect sizes using single nucleotide polymorphisms with minor alleles frequencies > 0.3. Of markers in TLR2, TLR5 and TLR9 that met these criteria, we found an association Family Based Association Tests [(FBAT) Z score = 4.232; p = 1.5 x 10-5; p corrected = 1.2 x 10-4] between the C allele (frequency = 0.424; odds ratio = 7; 95 percent confidence interval 1.6-30.8) of rs352140 at TLR9 and toxoplasmic retinochoroiditis in Brazil. This supports the hypothesis that direct interaction between T. gondii and TLR9 may trigger proinflammatory responses that lead to severe pathologies such as the ocular disease that is associated with this infection in Brazil.
Asunto(s)
Humanos , Polimorfismo de Nucleótido Simple/genética , Receptor Toll-Like 9/genética , Toxoplasmosis Ocular/genética , Brasil , Frecuencia de los Genes , Predisposición Genética a la EnfermedadRESUMEN
Toxoplasmosis is a worldwide zoonosis that generally produces an asymptomatic infection. In some cases, however, toxoplasmosis infection can lead to ocular damage. The immune system has a crucial role in both the course of the infection and in the evolution of toxoplasmosis disease. In particular, IFN-γ plays an important role in resistance to toxoplasmosis. Polymorphisms in genes encoding cytokines have been shown to have an association with susceptibility to parasitic diseases. The aim of this work was to analyse the occurrence of polymorphisms in the gene encoding IFN-γ (+874T/A) among Toxoplasma gondii seropositive individuals, including those with ocular lesions caused by the parasite, from a rural population of Santa Rita de Cássia, Barra Mansa, state of Rio de Janeiro, Brazil. Further, we verified which of these polymorphisms could be related to susceptibility to the development of ocular toxoplasmosis. This study included 34 individuals with ocular toxoplasmosis (ocular group) and 134 without ocular lesions (control group). The differences between A and T allele distributions were not statistically significant between the two groups. However, we observed that a higher frequency of individuals from the ocular group possessed the A/A genotype, when compared with the control group, suggesting that homozygocity for the A allele could enhance susceptibility to ocular toxoplasmosis in T. gondii infection.
Asunto(s)
Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Coriorretinitis/parasitología , Predisposición Genética a la Enfermedad/genética , Interferón gamma/genética , Toxoplasmosis Ocular/genética , Estudios de Casos y Controles , Coriorretinitis/genética , Coriorretinitis/inmunología , Frecuencia de los Genes , Genotipo , Polimorfismo de Nucleótido Simple , Población Rural , Toxoplasmosis Ocular/inmunología , Adulto JovenRESUMEN
Analysing human genetic variation provides a powerful tool in understanding risk factors for disease. Toxoplasma gondii acquired by the mother can be transmitted to the fetus. Infants with the most severe clinical signs in brain and eye are those infected early in pregnancy when fetal immunity is least well developed. Genetic analysis could provide unique insight into events in utero that are otherwise difficult to determine. We tested the hypothesis that propensity for T. gondii to cause eye disease is associated with genes previously implicated in congenital or juvenile onset ocular disease. Using mother-child pairs from Europe (EMSCOT) and child/parent trios from North America (NCCCTS), we demonstrated that ocular and brain disease in congenital toxoplasmosis associate with polymorphisms in ABCA4 encoding ATP-binding cassette transporter, subfamily A, member 4 previously associated with juvenile onset retinal dystrophies including Stargardt's disease. Polymorphisms at COL2A1 encoding type II collagen, previously associated with Stickler syndrome, associated only with ocular disease in congenital toxoplasmosis. Experimental studies showed that both ABCA4 and COL2A1 show isoform-specific epigenetic modifications consistent with imprinting, which provided an explanation for the patterns of inheritance observed. These genetic and epigenetic risk factors provide unique insight into molecular pathways in the pathogenesis of disease.
Asunto(s)
Femenino , Humanos , Recién Nacido , Embarazo , Transportadoras de Casetes de Unión a ATP/genética , Colágeno Tipo II/genética , Toxoplasmosis Cerebral/genética , Toxoplasmosis Congénita/genética , Toxoplasmosis Ocular/genética , Epigénesis Genética/genética , Genotipo , Polimorfismo de Nucleótido SimpleRESUMEN
A retinocoroidite toxoplásmica em irmäos näo gêmeos näo é rara na regiäo de Erechim, Rio Grande do Sul e corresponde a 7,8% dos casos de toxoplasmose ocular, atendidos de maio de 81 a maio de 84. O autor apresenta, família de seis irmäos näo gêmeos com retinocoroidite toxoplásmica, diagnosticada através de aspecto clínico das lesöes, sorologia positiva exclusivamente para toxoplasmose e exclusäo dos diagnósticos diferenciais. Três dos pacientes foram acompanhados pelo autor pelo período de 10 anos tendo ocorrido vários episódios de retinocoroidite toxoplásmica recorrente