RESUMO
BACKGROUND: Chronic Chagas Disease cardiomyopathy (CCC), a life-threatening inflammatory dilated cardiomyopathy, affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi, the rest of the infected subjects remaining asymptomatic (ASY). The Th1 T cell-rich myocarditis plays a pivotal role in CCC pathogenesis. Local expression of IL-18 in CCC myocardial tissue has recently been described. IL-18 could potentially amplify the process by inducing increased expression of IFN-γ which in turn can increase the production of IL-18, thereby creating a positive feedback mechanism. In order to assess the contribution of the IL-18 to susceptibility to Chronic Chagas Disease, we investigated the association between a single nucleotide polymorphism (SNP) located in the IL-18 gene with the risk of developing Chagas cardiomyopathy. METHODS AND RESULTS: We analyzed the rs2043055 marker in the IL18 gene in a cohort of Chagas disease cardiomyopathy patients (n=849) and asymptomatic subjects (n=202). We found a significant difference in genotype frequencies among moderate and severe CCC patients with ventricular dysfunction. CONCLUSIONS: Our analysis suggests that the IL18 rs2043055 polymorphism- or a SNP in tight linkage disequilibrium with it- may contribute to modulating the Chagas cardiomyopathy outcome.
Assuntos
Cardiomiopatia Chagásica/genética , Predisposição Genética para Doença , Interleucina-18/genética , Polimorfismo de Nucleotídeo Único/genética , Estudos de Casos e Controles , Cardiomiopatia Chagásica/fisiopatologia , Doença Crônica , Estudos de Coortes , Feminino , Estudos de Associação Genética , Humanos , Masculino , Volume SistólicoRESUMO
Background: Chronic Chagas Disease cardiomyopathy (CCC), a life-threatening inflammatory dilated cardiomyopathy,affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi, the restof the infected subjects remaining asymptomatic (ASY). The Th1 T cell-rich myocarditis plays a pivotalrole in CCC pathogenesis. Local expression of IL-18 in CCC myocardial tissue has recently been described.IL-18 could potentially amplify the process by inducing increased expression of IFN-c which in turn canincrease the production of IL-18, thereby creating a positive feedback mechanism. In order to assess thecontribution of the IL-18 to susceptibility to Chronic Chagas Disease, we investigated the associationbetween a single nucleotide polymorphism (SNP) located in the IL-18 gene with the risk of developingChagas cardiomyopathy.Methods and results: We analyzed the rs2043055 marker in the IL18 gene in a cohort of Chagas diseasecardiomyopathy patients (n = 849) and asymptomatic subjects (n = 202). We found a significant differencein genotype frequencies among moderate and severe CCC patients with ventricular dysfunction.Conclusions: Our analysis suggests that the IL18 rs2043055 polymorphism- or a SNP in tight linkagedisequilibrium with it- may contribute to modulating the Chagas cardiomyopathy outcome.
Assuntos
Disfunção Ventricular , Doença de Chagas , MiocarditeRESUMO
A morte súbita cardíaca (MSC) é um grave problema mundial, no entanto, não apenas no Brasil, mas em todo o mundo, estamos distantes de uma solução definitiva. Sua importância é determinada pelo impacto epidemiológico, potencial de ocorrência em população economicamente ativa e possibilidade de utilização de diferentes estratégias preventivas visando redução de sua incidência. Os caminhos para que o Sistema de Saúde Pública brasileiro solucione os problemas da MSC exigem: A - medidas assistenciais e educacionais, B - medidas burocráticas e de apoio à pesquisa. estratégias focando controle de fatores de risco, melhora da assistência aos cardiopatas, treinamento de profissionais da saúde e conscientização da população são necessárias para sua prevenção. A praticipação do Ministério da Sáude e das principais sociedades médicas brasileiras é essencial nestas intervenções. No Brasil, a melhora da gestão das ações e dos recursos financeiros, bem como a reestruturação de processos logísticos e recursos humanos para a melhora da assistência básica à saúde e de suporte à pesquisa devem ser aplicadas. Descrevemos, neste texto, as diferentes possibilidades de atuação na busca de soluções eficientes e factíveis para redução de sua incidência.
The sudden cardiac death (SCD) is a serious public health problem worldwide, however, not only in Brazil but worldwide we are far from a definitive solution. Its importance is determined by epidemiological impact, potential for occurence in the economically active population and the possibility of different preventive strategies. The paths to the Brazilian Public Health System to solve the MSC problem: A - care and educational measures, B - bureaucratic measures and research support. Strategies focusing on control of risk factors, improvement of assistance for heart disease patients, training of health professionals and public awareness are necessary for its prevention. The participation of the Ministry of Health and Brazilian medical societies is essential in these interventions. In Brazil, the improvement of management actions and financial resources, as well as the restructuring of logistics processes and human resources for improving basic health care and support for research should be applied. We describe in this paper the different possibilities to find feasible and efficient solutions to reduce its incidence.