Interferon-Inducible Transmembrane Protein 3 Genetic Variant rs12252 and Influenza Susceptibility and Severity: A Meta-Analysis

Xianxian Yang; Bin Tan; Xipeng Zhou; Jian Xue; Xian Zhang; Peng Wang; Chuang Shao; Yingli Li; Chaorui Li; Huiming Xia; Jingfu Qiu

doi:10.1371/journal.pone.0124985

Interferon-Inducible Transmembrane Protein 3 Genetic Variant rs12252 and Influenza Susceptibility and Severity: A Meta-Analysis

PLoS One. 2015 May 5;10(5):e0124985. doi: 10.1371/journal.pone.0124985. eCollection 2015.

Authors

Xianxian Yang¹, Bin Tan¹, Xipeng Zhou¹, Jian Xue¹, Xian Zhang¹, Peng Wang¹, Chuang Shao², Yingli Li¹, Chaorui Li¹, Huiming Xia³, Jingfu Qiu¹

Affiliations

¹ School of Public Health and Management, Chongqing Medical University, Chongqing, China.
² Department of inspection, The University-Town Affiliated Hospital of Chongqing Medical University, Chongqing, China.
³ School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.

Abstract

Background: The 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.

Methods: Relevant 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).

Results: A 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).

Conclusion: 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. The rs12252-C allele causes a 23.7% higher chance of infection and also constitutes a risk factor for more severe influenza.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Alleles*
Genetic Predisposition to Disease*
Genetic Variation*
Genotype
Humans
Influenza, Human / diagnosis*
Influenza, Human / genetics*
Membrane Proteins / genetics*
Odds Ratio
Polymorphism, Single Nucleotide
Publication Bias
RNA-Binding Proteins / genetics*
Severity of Illness Index

Substances

IFITM3 protein, human
Membrane Proteins
RNA-Binding Proteins

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (grant Nos. 31071093, 31170129, and 31200064). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.