IFITM3 rs12252 T>C polymorphism is associated with the risk of severe influenza: a meta-analysis

Abstract

The interferon-inducible transmembrane protein 3 (IFITM3), as one of the key genes involved in the interferon pathway, is critical for defending the host against influenza virus, and the rs12252 T>C variant in IFITM3 might be associated with susceptibility to severe influenza. Owing to contradictory and inconclusive results, we performed a meta-analysis to assess the association between rs12252 T>C polymorphism and severe influenza risk. A comprehensive literature search up to 1 August 2014 was conducted in EMBASE, Pubmed, Web of Science, VIP, Wanfang and CNKI databases. Four eligible studies with a total of 445 influenza patients and 3396 controls were included in this meta-analysis. Overall, our results demonstrated a significant association between the IFITM3 rs12252 T>C polymorphism and influenza risk [C vs. T: odds ratio (OR) 1·68, 95% confidence interval (CI) 1·32-2·13; CC vs. CT+TT: OR 2·38, 95% CI 1·52-3·73; CC+CT vs. TT: OR 1·62, 95% CI 1·18-2·22]. Stratification by ethnicity indicated that the variant C allele was associated with an 88% increased risk of influenza in Asians (C vs. T: OR 1·88, 95% CI 1·34-2·62). Moreover, subjects carrying the variant C allele had an increased risk of developing severe illness upon influenza infection (C vs. T: OR 2·70, 95% CI 1·86-3·94). However, no significant association was observed in patients with mild infection (C vs. T: OR 1·26, 95% CI 0·93-1·71). 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.

Mx genes: host determinants controlling influenza virus infection and trans-species transmission

“…The only alterations in a gene associated with severe seasonal influenza in hospitalized patients were two single nucleotide polymorphisms (SNP) in IFITM3. One, rs12252, leads to a truncation (Everitt et al 2012;Xuan et al 2015;Zhang et al 2013), and the other, rs34481144i, to diminished expression and impaired recruitment of immune CD8+ T cells into the infected airways (Allen et al 2017). Still, the role of IFITM3 in human influenza infections remains controversial (Mills et al 2014;Williams et al 2014;Zani and Yount 2018).…”

Influenza Pathogenesis: The Effect of Host Factors on Severity of Disease

“…Host genes associated with severe influenza virus in humans with severe IAV-H1H1 and IAV-H7N9 disease in some, but not all, cohorts(135)(136)(137)(138)(139)(140)(141)(142)(143)(144). rs34481144 was associated with reduced gene expression in CD8 + T cells and severe IAV disease(110).…”

No Correlation of the Disease Severity of Influenza A Virus Infection with the rs12252 Polymorphism of the Interferon-Induced Transmembrane Protein 3 Gene

“…However, for individuals with mild infection, no significant association was observed. These findings suggested that the rs12252T>C SNP is significantly correlated with an increased risk of severe influenza but not with the likelihood of early influenza infection [12] . The discrepancy between the results of Mills et al [10] and meta-analysis data may be due to differences in sample sizes, statistical power, and ethnic groups.…”