In recent years a single nucleotide polymorphism, interferon-induced transmembrane protein 3 (IFITM3) rs12252, has been shown to alter the severity of influenza infection in Asian populations.
By performing high-throughput RNA sequencing on primary dendritic cells and peripheral blood mononuclear cells isolated from pandemic H1N1 influenza and human immunodeficiency virus-1 (HIV-1) infected patients we show that full-length IFITM3 mRNA is dominantly expressed (>99%) across all rs12252 genotypes.
For each sample <i>IFITM3</i> rs12252 genotype was determined and antibody levels in response to pdmH1N1, H3N2 and Influenza B infection were measured for each time point.
Neither rs12252 nor rs8072510 showed an association according to the presence of clinical risk factors for influenza complications (P > 0.05), suggesting that these factors did not modify associations between the SNPs and hospitalized influenza.
Our results indicated increased risk of both severe and mild influenza in subjects carrying the IFITM3 rs12252 polymorphism in the allele contrast C vs. T: OR (severe) = 1.69, 95% CI = 1.23-2.33, P = 0.001, and OR (mild) = 1.46, 95% CI = 1.13-1.87, P = 0.004.
<b>Conclusion:</b><i>IFITM3</i> rs12252</span> CC genotype was associated with severity rather than susceptibility of IVI in Chinese population, and this strong effect was observed in all subtypes of seasonal influenza infection.
Previous studies have reported associations of IFITM3 SNP rs12252 with severe influenza, but evidence of association and the mechanism by which risk is conferred remain controversial.
Our meta-analysis suggests that IFITM3 rs12252 T>C polymorphism is significantly associated with increased risk of severe influenza but not with the chance of initial virus infection.
The single-nucleotide polymorphism rs12252-C, which is rare in Caucasian populations, but much more common in the Han Chinese population, has been found in much higher homozygous frequency in patients with severe acute influenza.
Our meta-analysis suggests a significant association between a minor IFITM3 allele (SNP rs12252-C) with severe influenza</span> susceptibility, but not in mild influenza subjects, in both UK Caucasians and Han Chinese population.
We found evidence of an association between rs12252 rare allele homozygotes and susceptibility to mild influenza (in patients attending primary care) but could not confirm a previously reported association between this single-nucleotide polymorphism and susceptibility to severe H1N1 infection.
They also suggested that mechanisms, other than viral entry restriction, might contribute to variations in clinical outcomes of H1N1 influenza associated with rs12252-C.
We find that a statistically significant number of hospitalized subjects show enrichment for a minor IFITM3 allele (SNP rs12252-C) that alters a splice acceptor site, and functional assays show the minor CC genotype IFITM3 has reduced influenza virus restriction in vitro.
Several studies suggest that the CC genotype at the single nucleotide polymorphism (SNP) rs12252 of IFITM3 confers a genetic predisposition to pandemic influenza A in Europeans and Han Chinese, although one study in a British cohort failed to show an association.
<i>IFITM3</i> rs12252-C was associated with severe influenza virus infection in several studies, however whether this association is universal to all types of influenza virus or diverse ethnic populations remain controversial.
The IFITM3 rs12252 variant was associated with respiratory infection hospitalization but not specifically in patients infected with Influenza A(H1N1)pdm09.
Our meta-analysis suggests that IFITM3 rs12252 T>C polymorphism is significantly associated with increased risk of severe influenza but not with the chance of initial virus infection.