Department of Paediatrics and Adolescent Medicine, University of Turku and Turku University Hospital, Turku, Finland.
Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland.
J Infect Dis. 2021 Jan 4;223(1):157-165. doi: 10.1093/infdis/jiaa341.
Genetic heterogeneity in type I interferon (IFN)-related gene IFI44L may account for variable susceptibility to respiratory tract infections (RTIs) in children.
In 2 prospective, population-based birth cohorts, the STEPS Study and the FinnBrain Birth Cohort Study, IFI44L genotypes for rs273259 and rs1333969 were determined in relation to the development of RTIs until 1 or 2 years of age, respectively. At age 3 months, whole-blood transcriptional profiles were analyzed and nasal samples were tested for respiratory viruses in a subset of children.
In the STEPS Study (n = 1135), IFI44L minor/minor gene variants were associated with lower rates of acute otitis media episodes (adjusted incidence rate ratio, 0.77 [95% confidence interval, .61-.96] for rs273259 and 0.74 [.55-.99] for rs1333969) and courses of antibiotics for RTIs (0.76 [.62-.95] and 0.73 [.56-.97], respectively. In the FinnBrain cohort (n = 971), IFI44L variants were associated with lower rates of RTIs and courses of antibiotics for RTIs. In respiratory virus-positive 3-month-old children, IFI44L gene variants were associated with decreased expression levels of IFI44L and several other IFN-related genes.
Variant forms of IFI44L gene were protective against early-childhood RTIs or acute otitis media, and they attenuated IFN pathway activation by respiratory viruses.
I 型干扰素（IFN）相关基因 IFI44L 的遗传异质性可能导致儿童呼吸道感染（RTI）易感性的差异。
在两项前瞻性、基于人群的出生队列研究中，即 STEPS 研究和芬兰脑出生队列研究中，分别针对 rs273259 和 rs1333969 位点的 IFI44L 基因型与儿童至 1 或 2 岁时 RTI 的发生发展进行了研究。在 3 个月大时，对一部分儿童的全血转录谱进行了分析，并对鼻样本进行了呼吸道病毒检测。
在 STEPS 研究（n=1135）中，IFI44L 次要/次要基因变异与急性中耳炎发作率降低相关（校正后的发病率比，rs273259 为 0.77 [95%置信区间，0.61-0.96]，rs1333969 为 0.74 [0.55-0.99]）和 RTI 抗生素疗程（0.76 [0.62-0.95]和 0.73 [0.56-0.97]）。在芬兰脑队列研究（n=971）中，IFI44L 变异与 RTI 发生率和 RTI 抗生素疗程减少相关。在 3 个月大的呼吸道病毒阳性儿童中，IFI44L 基因变异与 IFI44L 和其他几种 IFN 相关基因的表达水平降低有关。
IFI44L 基因的变异形式对婴幼儿 RTI 或急性中耳炎具有保护作用，并且减弱了呼吸道病毒对 IFN 通路的激活作用。
