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      Genetic polymorphism for IFNγ +874T/A in patients with acute toxoplasmosis Translated title: Polimorfismo genético para IFNγ +874T/A em pacientes com toxoplasmose aguda

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          Abstract

          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.

          Translated abstract

          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.

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          Most cited references15

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          An unusually high prevalence of ocular toxoplasmosis in southern Brazil.

          Because of the frequency of ocular toxoplasmosis and its occurrence in multiple siblings in southern Brazil, a population-based household survey was performed to better understand the epidemiologic characteristics of the disease in this region. Of 1,042 individuals examined, 184 (17.7%) were deemed to have ocular toxoplasmosis on the basis of conservative assessment of ophthalmic findings. Of those with ocular toxoplasmosis, 183 (99.5%) had specific IgG antibodies, compared with only 140 of 181 age-matched control subjects (77.4%; P less than .001). The prevalence of ocular toxoplasmosis was 0.9% in 1- to 8-year-olds, 4.3% in 9- to 12-year-olds, 14.3% in 13- to 16-year-olds, and 21.3% (95% confidence interval, 18.6% to 24.2%) in all individuals 13 years or older. The prevalence of ocular toxoplasmosis in this population was more than 30 times higher than previous estimates for the same condition elsewhere. The low prevalence in the young children we studied supplements previous data suggesting that, in this population, ocular toxoplasmosis is a sequela of postnatal rather than congenital infection.
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            A single nucleotide polymorphism in the first intron of the human IFN-gamma gene: absolute correlation with a polymorphic CA microsatellite marker of high IFN-gamma production.

            We have described previously a variable length CA repeat sequence in the first intron of the human IFN-gamma gene and showed that allele #2 is associated with high in vitro IFN-gamma production. In a consecutive study, allele #2 was found to be associated with allograft fibrosis in lung transplant patients, confirming its role as a marker of high IFN-gamma production, both in vivo and in vitro. In this study we have sequenced 50 PCR products that had been typed previously by PAGE for the identification of CA microsatellite alleles. We report on a novel single nucleotide polymorphism, T to A, at the 5' end of the CA repeat region in the first intron of the human IFN-gamma gene (+874*T/A). There is an absolute correlation between the presence of T allele and the presence of the high-producing microsatellite allele #2. This T to A polymorphism coincides with a putative NF-kappa B binding site which might have functional consequences for the transcription of the human IFN-gamma gene. Therefore, the T to A polymorphism could directly influence the level of IFN-gamma production associated with the CA microsatellite marker.
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              Interferon-gamma: the major mediator of resistance against Toxoplasma gondii.

              Mice were injected with a monoclonal antibody to interferon-gamma to examine the importance of endogenous production of this lymphokine in resistance against infection with the sporozoan parasite Toxoplasma gondii. Mice with intraperitoneal infections of T. gondii that received no antibody survived and developed chronic T. gondii infection, whereas the infected mice that received the monoclonal antibody died of toxoplasmosis. The activation of macrophages, which kill T. gondii in vivo, was inhibited by administration of the monoclonal antibody, but the production of antibodies to T. gondii was not suppressed. The fact that an antibody to interferon-gamma can eliminate resistance to acute Toxoplasma infection in mice suggests that this lymphokine is an important mediator of host resistance to this parasite.
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                Author and article information

                Journal
                rsbmt
                Revista da Sociedade Brasileira de Medicina Tropical
                Rev. Soc. Bras. Med. Trop.
                Sociedade Brasileira de Medicina Tropical - SBMT (Uberaba, MG, Brazil )
                0037-8682
                1678-9849
                December 2012
                : 45
                : 6
                : 757-760
                Affiliations
                [05] Rio de Janeiro RJ orgnameInstituto Oswaldo Cruz orgdiv1Laboratório de Epidemiologia Molecular de Doenças Infecciosas
                [03] Rio de Janeiro RJ orgnameEscola Nacional de Saúde Pública orgdiv1Fundação Oswaldo Cruz
                [02] Rio de Janeiro RJ orgnameInstituto Oswaldo Cruz orgdiv1Laboratório de Toxoplasmose
                [04] Rio de Janeiro RJ orgnameFundação Oswaldo Cruz orgdiv1Instituto de Pesquisa Clinica Evandro Chagas orgdiv2Laboratório de Imunologia e Imunogenética
                [01] Rio de Janeiro RJ orgnameFundação Oswaldo Cruz orgdiv1Instituto de Pesquisa Clinica Evandro Chagas orgdiv2Laboratório de Pesquisa Clínica em Doenças Febris Agudas
                Article
                S0037-86822012000600020 S0037-8682(12)04500620
                5ba9d57d-6f90-49d1-9a13-865b8e174beb

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 17 January 2011
                : 05 May 2011
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 15, Pages: 4
                Product

                SciELO Brazil

                Categories
                Short Communications

                Interferon-gama,Retinocoroidite,Toxoplasmose,Retinochoroiditis,Interferon gamma,Toxoplasmosis

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