Abstract
BackgroundThe pandemic influenza A (H1N1) pdm09 virus, avian influenza A (H5N1) virus, and influenza A (H7N9) virus induced severe morbidity and mortality throughout the world. Previous studies suggested a close association between the interferon-induced transmembrane protein-3 (IFITM3) genetic variant rs12252 and influenza. Here, we explored the correlation between the rs12252 and influenza susceptibility and severity using meta-analysis.MethodsRelevant studies published before May 22, 2014 were retrieved from PubMed, ISI web of knowledge, EBSCO, and Cochrane central register of controlled trials databases. Association between rs12252 and influenza susceptibility and severity were determined using statistical analysis of odds ratios (ORs).ResultsA total of four studies consisting of 445 cases and 4180 controls were included in our analysis. Generally, there is increased risk of influenza in subjects carrying rs12252 in the recessive model (CC vs. CT+TT: OR = 2.35, 95% CI: 1.49-3.70, P<0.001), the dominant model (CC+CT vs. TT: OR=1.60, 95% CI: 1.18–2.22, P=0.003), the homozygote comparison (CC vs. TT: OR=4.11, 95% CI: 2.15–7.84, P<0.001), and the allele contrast (C vs. T: OR=1.67, 95% CI: 1.32–2.13, P<0.001). Stratification analysis of ethnicity and severity revealed a significant increase in influenza susceptibility by IFITM3-SNP rs12252 among both Asian and Caucasian population. SNP rs12252 shows significant impact on severe infections (P<0.05), but not on mild influenza. Besides, our result also associated rs12252 with influenza severity (severe vs. mild: OR=2.37, 95% CI: 1.32–4.25, P=0.004), (severe vs. control: OR=2.70, 95% CI: 1.85–3.94, P<0.001).ConclusionOur meta-analysis suggests a significant association between a minor IFITM3 allele (SNP rs12252-C) with severe influenza susceptibility, but not in mild influenza subjects, in both UK Caucasians and Han Chinese population. The rs12252-C allele causes a 23.7% higher chance of infection and also constitutes a risk factor for more severe influenza.
Highlights
Stratification analysis of ethnicity and severity revealed a significant increase in influenza susceptibility by interferon-induced transmembrane protein-3 (IFITM3)-SNP rs12252among both Asian and Caucasian population
Our meta-analysis suggests a significant association between a minor IFITM3 allele (SNP rs12252-C) with severe influenza susceptibility, but not in mild influenza subjects, in both UK Caucasians and Han Chinese population
In the past decade, emerging and re-emerging epidemic diseases including H7N9 virus in China and the Middle-East-Respiratory-Syndrome (MERS)-coronavirus in the Middle East and Europe have strongly resembled the threat caused by the Severe Acute Respiratory Syndrome (SARS)-coronavirus, H1N1 virus, and H5N1 virus to human health
Summary
In the past decade, emerging and re-emerging epidemic diseases including H7N9 virus in China and the Middle-East-Respiratory-Syndrome (MERS)-coronavirus in the Middle East and Europe have strongly resembled the threat caused by the Severe Acute Respiratory Syndrome (SARS)-coronavirus, H1N1 virus, and H5N1 virus to human health. Influenza remains a major global health threat due to the high morbidity and mortality caused by seasonal epidemics as well as the wide variety of the virus. The risk factors of influenza included the intrinsic pathogenicity of the virus, acquired host factors (such as immunity and comorbidity) and intrinsic host susceptibility. The study of host genetic factors involved in susceptibility to influenza is a promising strategy that may identify potential therapeutic targets [2]. Systematical investigation of the association between host genetic factors and the occurrence of influenza is of pivotal importance. In 2009, the World Health Organization (WHO) identified studies of the role of host genetic factors on susceptibility to severe influenza as a priority [3]. We explored the correlation between the rs12252 and influenza susceptibility and severity using meta-analysis
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