Genetic susceptibility to respiratory syncytial virus bronchiolitis is predominantly associated with innate immune genes
Genetic susceptibility to respiratory syncytial virus bronchiolitis is predominantly associated with innate immune genes
复制标题
DOI：
10.1086/520886
复制
发表时间：
2007-09-15
影响因子：
6.4
通讯作者：
Hoebee, Barbara
中科院分区：
文献类型：
--
作者：
Janssen, Riny;Bont, Louis;Hoebee, Barbara
背景呼吸道合胞病毒（RSV）是婴儿严重下呼吸道感染的常见原因。只有一部分感染RSV的儿童需要住院治疗。由于已知的严重疾病的风险因素，如早产，不能完全解释疾病严重程度的差异，遗传因素已被牵连。方法.为了研究RSV易感性的复杂性，并确定其发展中涉及的基因和生物学途径，我们进行了一项遗传关联研究，涉及470名因RSV毛细支气管炎住院的儿童，他们的父母和1008名随机人群对照。我们分析了220个候选基因的384个单核苷酸多态性（SNP），这些基因涉及气道粘膜反应、先天免疫趋化性、适应性免疫和过敏性哮喘。结果先天性免疫基因VDR（rs 10735810; P = .0017）、JUN（rs 11688; P = .0093）、IFNA 5（rs 10757212; P = .0093）和NOS 2（rs 1060826; P = .0031）中的SNP表现出与毛细支气管炎的最强关联。除了在等位基因水平上的关联，这4个SNP还在基因型水平上表现出关联（VDR、JUN、IFNA 5和NOS 2中的SNP分别为P = 0.0056、P = 0.0285、P = 0.0372和P = 0.0117）。先天免疫作为一个过程的作用是加强了整个集团的先天免疫单核苷酸多态性的关联时，全球测试组的基因（P = 0.046）。先天免疫基因中的SNP在确定RSV毛细支气管炎的易感性中是重要的。
Background. Respiratory syncytial virus (RSV) is a common cause of severe lower respiratory tract infection in infants. Only a proportion of children infected with RSV require hospitalization. Because known risk factors for severe disease, such as premature birth, cannot fully explain differences in disease severity, genetic factors have been implicated. Methods. To study the complexity of RSV susceptibility and to identify the genes and biological pathways involved in its development, we performed a genetic association study involving 470 children hospitalized for RSV bronchiolitis, their parents, and 1008 random, population controls. We analyzed 384 single - nucleotide polymorphisms (SNPs) in 220 candidate genes involved in airway mucosal responses, innate immunity chemotaxis, adaptive immunity, and allergic asthma. Results. SNPs in the innate immune genes VDR (rs10735810; P = .0017), JUN (rs11688; P = .0093), IFNA5 (rs10757212; P = .0093), and NOS2 (rs1060826; P = .0031) demonstrated the strongest association with bronchiolitis. Apart from association at the allele level, these 4 SNPs also demonstrated association at the genotype level (P = .0056, P = .0285, P = .0372, and P = .0117 for the SNPs in VDR, JUN, IFNA5, and NOS2, respectively). The role of innate immunity as a process was reinforced by association of the whole group of innate immune SNPs when the global test for groups of genes was applied (P = .046) Conclusion. SNPs in innate immune genes are important in determining susceptibility to RSV bronchiolitis.