Hospitalization Risk Due to Respiratory Illness Associated with Genetic Variation at IFITM3 in Patients with Influenza A(H1N1)pdm09 Infection: A Case-Control Study

Abstract

BackgroundRecent studies suggest an association between the Interferon Inducible Transmembrane 3 (IFITM3) rs12252 variant and the course of influenza infection. However, it is not clear whether the reported association relates to influenza infection severity. The aim of this study was to estimate the hospitalization risk associated with this variant in Influenza Like Illness (ILI) patients during the H1N1 pandemic influenza.MethodsA case-control genetic association study was performed, using nasopharyngeal/oropharyngeal swabs collected during the H1N1 pandemic influenza. Laboratory diagnosis of influenza infection was performed by RT-PCR, the IFITM3 rs12252 was genotyped by RFLP and tested for association with hospitalization. Conditional logistic regression was performed to calculate the confounder-adjusted odds ratio of hospitalization associated with IFITM3 rs12252.ResultsWe selected 312 ILI cases and 624 matched non-hospitalized controls. Within ILI Influenza A(H1N1)pdm09 positive patients, no statistical significant association was found between the variant and the hospitalization risk (Adjusted OR: 0.73 (95%CI: 0.33–1.50)). Regarding ILI Influenza A(H1N1)pdm09 negative patients, CT/CC genotype carriers had a higher risk of being hospitalized than patients with TT genotype (Adjusted OR: 2.54 (95%CI: 1.54–4.19)).ConclusionsThe IFITM3 rs12252 variant was associated with respiratory infection hospitalization but not specifically in patients infected with Influenza A(H1N1)pdm09.

Interferon-Induced Transmembrane Protein 3 Inhibits Hantaan Virus Infection, and Its Single Nucleotide Polymorphism rs12252 Influences the Severity of Hemorrhagic Fever with Renal Syndrome

“…We demonstrated that truncated IFITM3 protein also loses the ability to inhibit HTNV infection in vitro. In Northern European patients hospitalized with seasonal influenza or pandemic influenza A virus, increased homozygosity of the minor C allele of SNP rs12252 in IFITM3 was observed (37). In Chinese patients infected with influenza A (H1N1) virus, there was also an increased frequency of the C allele and CC genotype of SNP rs12252 (13).…”

IFITM3, TLR3, and CD55 Gene SNPs and Cumulative Genetic Risks for Severe Outcomes in Chinese Patients With H7N9/H1N1pdm09 Influenza

“…The success rates were not significantly different among the target genes and participating institutes. At the time of writing, a study on IFITM3 SNP was published, reporting a similar genotyping success rate of 87% using archived respiratory tract samples collected from patients with influenza-like illnesses [27].…”

“…The SNP of CD55 rs2564978 has been associated (indirectly) with decreased promotor activity and lowered protection level [8,24,25]. Results of these SNPs' associations with clinical severity, however, appear to be inconsistent, and likely confounded by patients' ethnicity, clinical characteristics, antiviral treatment, and small sample sizes; further, the impacts on survival had not been examined [17,20,21,[25][26][27]. Notably, some of these genetic variants are much more prevalent among the East Asian populations, thus potentially exerting stronger impacts than in populations where their frequencies are low (eg, those with European ancestries) [15,17,24].…”

Role of rhesus macaque IFITM3(2) in simian immunodeficiency virus infection of macaques

“…They were also found to progress faster towards AIDS [37]. These findings, although not undisputed (see [38][39][40][41][42][43] for examples), indicates that polymorphisms in huIFITM3 can impact the course of viral infections. This notion has recently been reinforced by the finding that a polymorphism in the huI-FITM3 promoter that reduces IFITM3 expression increases the risk for severe influenza [44,45].…”