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INVESTIGATION OF HUMAN IFITM3 POLYMORPHISMS RS34481144A AND RS12252C AND RISK FOR INFLUENZA A(H1N1)PDM09 SEVERITY IN A BRAZILIAN COHORT
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Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratórios e do Sarampo. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Desenvolvimento Tecnológico em Virologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratórios e do Sarampo. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratórios e do Sarampo. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratórios e do Sarampo. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Desenvolvimento Tecnológico em Virologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratórios e do Sarampo. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratórios e do Sarampo. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratórios e do Sarampo. Rio de Janeiro, RJ, Brasil.
Abstract
Influenza is a major public health problem that causes acute respiratory infection in
humans. Identification of host factors influencing in disease outcome is critical for
recognition of individuals with increased risk. Investigations on the role of rs34481144A
and rs12252C IFITM3 polymorphisms in influenza A(H1N1)pdm09 severity is not yet
conclusively determined. This study aimed to evaluate such polymorphisms frequencies
and IFITM3 levels in an infected Brazilian cohort of 314 influenza A(H1N1)pdm09 cases
and its putative association with clinical, epidemiological and virological data. Individuals
were clinically classified into mild, severe and fatal cases. IFITM3 polymorphisms were
detected by specific Taqman probes in real time PCR reactions. IFITM3 levels were
determined by quantitative real time PCR. Thus, the different clinical groups presented
similar distribution of rs34481144 and rs12252 genotypes and allelic frequencies. There
was no significant association between the polymorphisms with severity of disease by
using distinct genetic models. Additionally, geographic distribution of mutants showed
that rs34481144A allele was more predominant in Brazilian Southern region. In contrast,
rs12252C allele presented similar frequencies in all regions. Individuals with the distinct
rs34481144 and rs12252 genotypes showed similar levels of IFITM3 and viral load in
their respiratory specimens. Furthermore, IFITM3 levels were comparable in the distinct
clinical groups and were not correlated with influenza viral load in analyzed samples.
Thereby, rs34481144A and rs12252C polymorphisms were not associated with severity
or mortality of influenza A(H1N1)pdm09 infection nor with IFITM3 transcript levels and
influenza viral load in upper respiratory tract samples in a Brazilian cohort.
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