Randolph Adrienne G, Yip Wai-Ki, Allen Emma Kaitlynn, Rosenberger Carrie M, Agan Anna A, Ash Stephanie A, Zhang Yu, Bhangale Tushar R, Finkelstein David, Cvijanovich Natalie Z, Mourani Peter M, Hall Mark W, Su Helen C, Thomas Paul G
Department of Anesthesia, Perioperative and Pain Medicine, Boston Children's Hospital.
Departments of Anaesthesia and Pediatrics, Harvard Medical School, Boston.
J Infect Dis. 2017 Jul 1;216(1):14-21. doi: 10.1093/infdis/jix242.
Interferon-induced transmembrane protein 3 (IFITM3) restricts endocytic fusion of influenza virus. IFITM3 rs12252_C, a putative alternate splice site, has been associated with influenza severity in adults. IFITM3 has not been evaluated in pediatric influenza.
The Pediatric Influenza (PICFLU) study enrolled children with suspected influenza infection across 38 pediatric intensive care units during November 2008 to April 2016. IFITM3 was sequenced in patients and parents were genotyped for specific variants for family-based association testing. rs12252 was genotyped in 54 African-American pediatric outpatients with influenza (FLU09), included in the population-based comparisons with 1000 genomes. Splice site analysis of rs12252_C was performed using PICFLU and FLU09 patient RNA.
In PICFLU, 358 children had influenza infection. We identified 22 rs12252_C homozygotes in 185 white non-Hispanic children. rs12252_C was not associated with influenza infection in population or family-based analyses. We did not identify the Δ21 IFITM3 isoform in RNAseq data. The rs12252 genotype was not associated with IFITM3 expression levels, nor with critical illness severity. No novel rare IFITM3 functional variants were identified.
rs12252 was not associated with susceptibility to influenza-related critical illness in children or with critical illness severity. Our data also do not support it being a splice site.
干扰素诱导跨膜蛋白3（IFITM3）可限制流感病毒的内吞融合。IFITM3 rs12252_C是一个假定的可变剪接位点，与成人流感严重程度相关。尚未对儿童流感中的IFITM3进行评估。
儿童流感（PICFLU）研究纳入了2008年11月至2016年4月期间38个儿科重症监护病房中疑似流感感染的儿童。对患者的IFITM3进行测序，并对父母进行特定变体的基因分型以进行基于家系的关联测试。对54名患有流感的非裔美国儿科门诊患者（FLU09）进行rs12252基因分型，纳入与千人基因组的人群比较。使用PICFLU和FLU09患者RNA对rs12252_C进行剪接位点分析。
在PICFLU中，358名儿童患有流感感染。我们在185名非西班牙裔白人儿童中鉴定出22名rs12252_C纯合子。在人群或基于家系的分析中，rs12252_C与流感感染无关。我们在RNAseq数据中未鉴定出Δ21 IFITM3异构体。rs12252基因型与IFITM3表达水平无关，也与危重病严重程度无关。未鉴定出新的罕见IFITM3功能变体。
rs12252与儿童流感相关危重病的易感性或危重病严重程度无关。我们的数据也不支持它是一个剪接位点。
