Hoebee Barbara, Bont Louis, Rietveld Edwin, van Oosten Marijke, Hodemaekers Hennie M, Nagelkerke Nico J D, Neijens Herman J, Kimpen Jan L L, Kimman Tjeerd G
Laboratory of Toxicology, Pathology, and Genetics, National Institute of Public Health and the Environment, Bilthoven, The Netherlands.
J Infect Dis. 2004 Jan 15;189(2):239-47. doi: 10.1086/380908. Epub 2004 Jan 9.
Previously, we reported genetic associations between severe respiratory syncytial virus (RSV) bronchiolitis in infants and polymorphisms in the interleukin (IL)-4 and IL-4 receptor alpha (IL-4Ralpha) genes, providing evidence for involvement of T helper type 2 cytokines in the pathogenesis of RSV bronchiolitis. We expanded our studies to polymorphisms in genes encoding IL-9, IL-10, and tumor necrosis factor (TNF)-alpha, using both a transmission/disequilibrium test and a case-control approach. Children homozygous for the IL-10 -592C or -592A allele had a higher risk of hospitalization for RSV bronchiolitis than did heterozygous carriers (odds ratio [OR], 1.73 vs. 2.55; 95% confidence interval [CI], 1.13-2.66 vs. 1.21-5.39). In children hospitalized at < or =6 months of age, a significant association between RSV bronchiolitis and the IL-10 -592C allele was found (OR, 1.61; 95% CI, 1.10-2.35). No significant associations of TNF-alpha and IL-9 polymorphisms with RSV bronchiolitis were observed. We also explored the interactions between different polymorphisms and found an interaction between the IL-4Ralpha Q551R and IL-10 C-592A polymorphisms.
此前，我们报道了婴儿严重呼吸道合胞病毒（RSV）细支气管炎与白细胞介素（IL）-4和IL-4受体α（IL-4Rα）基因多态性之间的遗传关联，为2型辅助性T细胞细胞因子参与RSV细支气管炎的发病机制提供了证据。我们使用传递/不平衡检验和病例对照方法，将研究扩展到编码IL-9、IL-10和肿瘤坏死因子（TNF）-α的基因多态性。IL-10 -592C或-592A等位基因纯合子的儿童因RSV细支气管炎住院的风险高于杂合子携带者（优势比[OR]，分别为1.73和2.55；95%置信区间[CI]，分别为1.13 - 2.66和1.21 - 5.39）。在≤6个月龄住院的儿童中，发现RSV细支气管炎与IL-10 -592C等位基因之间存在显著关联（OR，1.61；95% CI，1.10 - 2.35）。未观察到TNF-α和IL-9多态性与RSV细支气管炎之间存在显著关联。我们还探讨了不同多态性之间的相互作用，发现IL-4Rα Q551R和IL-10 C-592A多态性之间存在相互作用。
