Cellular Virology Laboratory, Department of Biological Sciences, Indian Institute of Science Education and Research (IISER), Mohali, India.
Cellular Virology Laboratory, Department of Biological Sciences, Indian Institute of Science Education and Research (IISER), Mohali, India.
Gene. 2018 Oct 20;674:70-79. doi: 10.1016/j.gene.2018.06.070. Epub 2018 Jun 22.
Intrinsic host susceptibility to viral infections plays a major role in determining infection severity in different individuals. In human influenza virus infections, multiple genetic association studies have identified specific human gene variants that might contribute to enhanced susceptibility or resistance to influenza. Recent studies suggested, the rs12252 T > C polymorphism in the interferon-inducible transmembrane protein 3 (IFITM3) gene might be associated with susceptibility to severe influenza. However, the studies reported conflicting and inconclusive results. To resolve the controversy, we conducted a systematic meta-analysis to evaluate the role of the IFITM3 rs12252 polymorphism in influenza susceptibility and severity, including twelve studies published before February 19, 2018 with a total 16,263 subjects (1836 influenza cases and 14,427 controls). Odds ratios (OR) and 95% confidence intervals were used to assess the strength of the association. 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. Similar results were obtained in the homozygote comparison and dominant model. Stratified analyses by ethnicity revealed increased risk of severe influenza in both the White and East Asian populations, but significant association with mild influenza was found only in the White population. Overall, our meta-analysis suggests a significant association between the IFITM3 rs12252 polymorphism and the risk of influenza in both the White and East Asian populations.
宿主对病毒感染的固有易感性在不同个体的感染严重程度中起着重要作用。在人类流感病毒感染中，多项遗传关联研究已经确定了特定的人类基因变异，这些变异可能导致对流感的易感性增强或抵抗力增强。最近的研究表明，干扰素诱导跨膜蛋白 3 (IFITM3) 基因中的 rs12252T > C 多态性可能与严重流感的易感性有关。然而，这些研究报告的结果相互矛盾，没有定论。为了解决这一争议，我们进行了一项系统的荟萃分析，以评估 IFITM3 rs12252 多态性与流感易感性和严重程度的关系，包括 2018 年 2 月 19 日之前发表的 12 项研究，共纳入 16263 例受试者（1836 例流感病例和 14427 例对照）。比值比 (OR) 和 95%置信区间用于评估关联的强度。我们的结果表明，在携带 IFITM3 rs12252 多态性的受试者中，无论是严重流感还是轻度流感的风险均增加：OR（严重）=1.69，95%CI=1.23-2.33，P=0.001，OR（轻度）=1.46，95%CI=1.13-1.87，P=0.004。在纯合子比较和显性模型中也得到了相似的结果。按种族进行分层分析显示，严重流感的风险在白人和东亚人群中均增加，但仅在白人人群中发现与轻度流感显著相关。总体而言，我们的荟萃分析表明，IFITM3 rs12252 多态性与白人和东亚人群流感的风险之间存在显著关联。
