Marr Nico, Hirschfeld Aaron F, Lam Angie, Wang Shirley, Lavoie Pascal M, Turvey Stuart E
Department of Pediatrics, University of British Columbia, Child and Family Research Institute, Vancouver, British Columbia, Canada.
PLoS One. 2014 Jun 20;9(6):e100269. doi: 10.1371/journal.pone.0100269. eCollection 2014.
The majority of cases of severe pediatric respiratory syncytial virus (RSV) infection occur in otherwise healthy infants who have no identifiable risk factors, suggesting that additional subclinical factors, such as population genetic variation, influence the course of RSV infection. The objective of this study was to test if common single nucleotide polymorphisms (SNPs) in genes encoding for immune signalling components of the RIG-I-like receptor (RLR) and IL-4-signalling pathways affect the outcome of RSV infection in early life. We genotyped 8 SNPs using allele-specific probes combined with real-time PCR. Each of the SNPs tested had previously been established to have a functional impact on immune responsiveness and two of the SNPs in the IL4 and IL4R genes had previously been associated with severe RSV bronchiolitis. Association with susceptibility to severe RSV infection was tested by statistically comparing genotype and allele frequencies in infants and young children hospitalized with severe RSV bronchiolitis (n = 140) with two control groups-children who tested positive for RSV but did not require hospitalization (n = 100), and a general population control group (n = 285). Our study was designed with sufficient power (>80%) to detect clinically-relevant associations with effect sizes ≥1.5. However, we detected no statistically significant differences in allele and genotype frequencies of the investigated SNPs between the inpatient and control groups. To conclude, we could not replicate the previously reported association with SNPs in the IL4 and IL4R genes in our independent cohort, nor did we find that common SNPs in genes encoding for RLRs and the downstream adapter MAVS were associated with susceptibility to severe RSV infections. Despite the existing evidence demonstrating a functional immunological impact of these SNPs, our data suggest that the biological effect of each individual SNP is unlikely to affect clinical outcomes of RSV infection.
大多数严重的小儿呼吸道合胞病毒（RSV）感染病例发生在无明显危险因素的健康婴儿中，这表明其他亚临床因素，如群体遗传变异，会影响RSV感染的病程。本研究的目的是测试编码视黄酸诱导基因I样受体（RLR）和白细胞介素4（IL-4）信号通路免疫信号成分的基因中的常见单核苷酸多态性（SNP）是否会影响早期RSV感染的结果。我们使用等位基因特异性探针结合实时PCR对8个SNP进行基因分型。之前已确定所测试的每个SNP对免疫反应性有功能影响，并且IL4和IL4R基因中的两个SNP之前与严重的RSV细支气管炎相关。通过统计学比较因严重RSV细支气管炎住院的婴幼儿（n = 140）与两个对照组（RSV检测呈阳性但无需住院的儿童，n = 100；以及一般人群对照组，n = 285）的基因型和等位基因频率，来测试与严重RSV感染易感性的关联。我们的研究设计具有足够的效能（>80%）来检测效应大小≥1.5的临床相关关联。然而，我们在住院患者组和对照组之间未检测到所研究SNP的等位基因和基因型频率存在统计学上的显著差异。总之，我们无法在我们的独立队列中重现之前报道的IL4和IL4R基因SNP的关联，也未发现编码RLR和下游衔接蛋白线粒体抗病毒信号蛋白（MAVS）的基因中的常见SNP与严重RSV感染易感性相关。尽管现有证据表明这些SNP具有功能性免疫影响，但我们的数据表明每个个体SNP的生物学效应不太可能影响RSV感染的临床结果。
