Estaria o polimorfismo 55MM da PON1 associado à maior gravidade da doença em pacientes com imunodeficiência comum variável?
Would the PON1-55MM polymorphism be associated to higher disease severity in patients with Common Variable Immunodeficiency?
Bruno Carnevale Sini; Sérgio Paulo Bydlowski; Débora Levy; Cristina M. Kokron; Luciana M. F. Maselli; Andrea Cohon; Ana Karolina Barreto de Oliveira; Jorge Kalil; Myrthes A. M. T. Barros
Resumo
Objetivo: Investigar a presença dos polimorfismos Q192R e L55M no gene da Paraoxonase1 (PON1) em pacientes com imunodeficiência comum variável (ICV) e sua relação com morbidade e gravidade da doença. Métodos: Pacientes com ICV e controles saudáveis foram genotipados para os polimorfismos L55M da PON1 e avaliados em relação à atividade arilesterase. No grupo de pacientes foram analisados parâmetros de morbidade e gravidade da doença. Resultados: O genótipo 55MM e o alelo 55M foram mais frequentes no grupo ICV em relação ao grupo controle. Pacientes com o genótipo 55MM apresentaram menor atividade de PON1, associada a maior morbidade da doença representada pela maior frequência de infecções de vias aéreas e taxa de internações. Por outro lado, a análise dos alelos demonstrou que a menor morbidade foi associada à presença do alelo 55L, que também apresentou relação com menor frequência de hiperplasia nodular linfoide (p = 0,007) e linfonodomegalia (p = 0,003) e menor ocorrência de óbitos (p = 0,039). Não foi observada relação entre a presença de alelos ou genótipos do polimorfismo PON1 Q192R e a maioria dos parâmetros avaliados neste estudo. Conclusões: Este constitui o primeiro relato da maior frequência do polimorfismo 55MM da PON1 em pacientes com ICV. Nossos resultados sugerem que o alelo 55L pode estar associado a um melhor prognóstico. Por outro lado, os resultados são sugestivos de que a presença do genótipo 55MM pode ser preditiva de maior morbidade e mortalidade em pacientes com ICV.
Palavras-chave
Abstract
Objective: To investigate the presence of Q192R e L55M polymorphisms on paraoxonase (PON1) gene, and the relationship of these polymorphisms to increased severity and morbidity of disease, among patients with Common Variable Immunodeficiency (CVID). Methods: Sixtyone patients diagnosed with CVID and 130 healthy control individuals underwent genotyping for the polymorphisms of PON1 and assaying for PON1 arylesterase activity. Patients were also evaluated for morbidity and severity parameters of the disease. Results: The 55MM genotype and the 55M allele were more frequent in the CVID group as compared to the control group. Patients with genotype 55MM had lower PON1 arylesterase activity, associated to higher morbidity represented by higher frequency of infection and of hospitalization rates. On the other hand, presence of the 55L allele was associated with lower morbidity, with lower frequency of nodular lymphoid hyperplasia and lymphadenopathy, and fewer deaths. There was no correlation of Q192R polymorphisms and the presence of any of the parameters evaluated in this study. Conclusions: This is the first report of increased frequency of L55M-PON1 polymorphisms in patients with CVID. Our results suggest that the presence of the 55L allele may be associated with a better prognosis. On the other hand, the results suggest that the presence of 55MM genotype may be predictive of higher morbidity and mortality in ICV patients.
Keywords
References
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Submitted date:
09/26/2014
Accepted date:
04/12/2015
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