Department of Pediatrics, University Teaching Hospital, Feldkirch, Austria.
PLoS One. 2009 Oct 7;4(10):e7374. doi: 10.1371/journal.pone.0007374.
Carriage of Neisseria meningitidis occurs approximately in 10% of the population, onset of invasive meningococcal disease (IMD) cannot be predicted and differs between ages. It remains unclear, which host factors determine invasion of the bloodstream by the bacteria. Innate immunity has a very important role in the first recognition of invading pathogens. The functional single nucleotide polymorphisms (SNPs) CD14 C-159T and toll-like receptor 4 (TLR4) Asp299Gly have been associated with the risk of gram-negative infections. However, their role in development of IMD still remains unclear. Our aim was to investigate the influence of CD14 C-159T and TLR4 Asp299Gly polymorphisms on the risk of IMD.
METHODOLOGY/PRINCIPAL FINDINGS: It was a retrospective case control study. Surviving Austrian meningococcal disease patients were enrolled by sending buccal swabs for DNA analysis. 185 cases with a proven meningococcal infection and 770 healthy controls were enrolled. In surviving meningococcal disease patients DNA analysis of CD14 C-159T and TLR 4 Asp299Gly polymorphisms was performed, as they are part of the innate immune response to bacterial determinants. CD14 C-159T and TLR4 Asp299Gly SNPs were not significantly associated with the presence of IMD when compared to healthy controls. The odds ratio for CD14 C-159T SNP was 1.14 (95% confidence interval (CI) 0.91-1.43; p = 0.266). In TLR4 Asp 299 Gly SNP the odds ratio was 0.78 (CI 0.47-1.43; p = 0.359).
CONCLUSION/SIGNIFICANCE: We could not observe a significant influence of CD14 C-159T and TLR4 Asp299Gly polymorphisms on the risk of developing IMD in surviving meningococcal disease patients. To our knowledge, this is the first study investigating the influence of the CD14 C-159T SNP on the susceptibility to IMD.
脑膜炎奈瑟菌的携带率约为人群的 10%，侵袭性脑膜炎球菌病（IMD）的发病不能预测，且在不同年龄段有所差异。目前尚不清楚哪些宿主因素决定了细菌侵入血流。先天免疫在识别入侵病原体方面起着非常重要的作用。功能性单核苷酸多态性（SNP）CD14 C-159T 和 toll 样受体 4（TLR4）Asp299Gly 与革兰氏阴性感染的风险相关。然而，它们在 IMD 发展中的作用仍不清楚。我们的目的是研究 CD14 C-159T 和 TLR4 Asp299Gly 多态性对 IMD 风险的影响。
方法/主要发现：这是一项回顾性病例对照研究。通过寄送口腔拭子进行 DNA 分析，招募幸存的奥地利脑膜炎球菌病患者。共纳入 185 例确诊的脑膜炎球菌感染患者和 770 例健康对照者。对幸存的脑膜炎球菌病患者进行 CD14 C-159T 和 TLR 4 Asp299Gly 多态性的 DNA 分析，因为它们是先天免疫对细菌决定簇反应的一部分。与健康对照组相比，CD14 C-159T 和 TLR4 Asp299Gly SNP 与 IMD 的发生无显著相关性。CD14 C-159T SNP 的比值比为 1.14（95%置信区间（CI）0.91-1.43；p=0.266）。TLR4 Asp299Gly SNP 的比值比为 0.78（CI 0.47-1.43；p=0.359）。
结论/意义：我们没有观察到 CD14 C-159T 和 TLR4 Asp299Gly 多态性对幸存的脑膜炎球菌病患者发生 IMD 风险的显著影响。据我们所知，这是第一项研究 CD14 C-159T SNP 对 IMD 易感性影响的研究。
