Genetic variation at the IFITM3 and Influenza A(H1N1)pdm09 infection severity in the Portuguese population

Abstract

Interferon-inducible transmembrane protein (IFITM3) inhibits the entry of viruses to the host cell, mediating resistance to influenza infection. It has been demonstrated that a genetic variation in the IFITM3 gene (rs12252) alters a splice-site, originating a protein with reduced activity. In this context, our aim was to determine if the C allele of the IFITM3 rs12252 polymorphism is associated with influenza infection or hospitalizations related to Influenza A(H1)pdm09 in the Portuguese population. To achieve our goal, a case-control study design was developed using the nasal swabs collected during the 2009 pandemic, on the context of the National Influenza Surveillance Program. Non-hospitalized influenza cases were defined as patients with influenza like illness (ILI) who tested positive for influenza A(H1)pdm09 and did not require hospitalization. Hospitalized-influenza cases were defined as ILI patients who tested positive for A(H1)pdm09 infection and who were hospitalized. For these cases groups two types of controls were selected: non-hospitalized ILI cases negative for A(H1)pdm09 and hospitalized ILI patients negative for A(H1)pdm09 infection. We have therefore selected 212 non-hospitalized influenza cases, 96 hospitalized influenza cases, 403 non-hospitalized negative controls and 198 hospitalized negative controls. We found that hospitalized negative controls had the highest frequency of allele C carriers (22.5%) and the lowest frequency was found among the non-hospitalized negative controls (11.11%). No association was found between testing positive for A(H1)pdm09 infection (susceptibility to infection) and the C allele of rs12252. We have also found that the risk of being hospitalized (independently of infection status) for the allele C carriers is the highest, after adjustment for age and gender, (OR: 1.59 (95% CI: 1.05-2.43). Our results suggest that the allele C of the IFITM3 rs122252 polymorphism was associated with respiratory disease hospitalizations but not specifically associated with the infection by Influenza A(H1N1)pdm09