Center for Microbial Pathogenesis, Department of Pediatrics, College of Medicine, The Research Institute at Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, United States of America.
Department of Microbiology and Immunology, School of Medicine, University of California Davis, Davis, California, United States of America.
PLoS One. 2014 May 27;9(5):e98269. doi: 10.1371/journal.pone.0098269. eCollection 2014.
As there is increasing evidence that aberrant defensin expression is related to susceptibility for infectious disease and inflammatory disorders, we sought to determine if copy number of the beta-defensin gene cluster located on chromosome 8p23.1 (DEFB107, 106, 105, 104, 103, DEFB4 and SPAG11), that shows copy number variation as a block, was associated with susceptibility to otitis media (OM). The gene DEFB103 within this complex encodes human beta defensin-3 (hBD-3), an antimicrobial peptide (AP) expressed by epithelial cells that line the mammalian airway, important for defense of mucosal surfaces and previously shown to have bactericidal activity in vitro against multiple human pathogens, including the three that predominate in OM. To this end, we conducted a retrospective case-control study of 113 OM prone children and 267 controls aged five to sixty months. We identified the copy number of the above defined beta-defensin gene cluster (DEFB-CN) in each study subject by paralogue ratio assays. The mean DEFB-CN was indistinguishable between subjects classified as OM prone based on a recent history of multiple episodes of OM and control subjects who had no history of OM (4.4 ± 0.96 versus 4.4 ± 1.08, respectively: Odds Ratio [OR]: 1.16 (95% CI: 0.61, 2.20). Despite a lack of direct association, we observed a statistically significant correlation between DEFB-CN and nasopharyngeal bacterial colonization patterns. Collectively, our findings suggested that susceptibility to OM might be mediated by genetic variation among individuals, wherein a DEFB-CN less than 4 exerts a marked influence on the microbiota of the nasopharynx, specifically with regard to colonization by the three predominant bacterial pathogens of OM.
由于越来越多的证据表明防御素表达异常与易感性传染病和炎症性疾病有关，我们试图确定位于 8p23.1 染色体上的β-防御素基因簇（DEFB107、106、105、104、103、DEFB4 和 SPAG11）的拷贝数是否与中耳炎（OM）易感性相关。该基因簇内的基因 DEFB103 编码人类β防御素-3（hBD-3），这是一种由哺乳动物气道上皮细胞表达的抗菌肽（AP），对黏膜表面的防御至关重要，并且先前已显示对多种人类病原体具有体外杀菌活性，包括 OM 中三种主要病原体。为此，我们对 113 名 OM 易感儿童和 267 名 5 至 60 个月的对照儿童进行了回顾性病例对照研究。我们通过等位基因比例测定法确定了每个研究对象上述定义的β-防御素基因簇（DEFB-CN）的拷贝数。根据近期多次 OM 发作的病史和无 OM 病史的对照组，分类为 OM 易感的受试者之间的平均 DEFB-CN 没有区别（分别为 4.4 ± 0.96 和 4.4 ± 1.08：比值比 [OR]：1.16（95%CI：0.61，2.20）。尽管没有直接关联，但我们观察到 DEFB-CN 与鼻咽细菌定植模式之间存在统计学上显著的相关性。总的来说，我们的发现表明，OM 的易感性可能是由个体之间的遗传变异介导的，其中 DEFB-CN 小于 4 会对鼻咽微生物群产生显著影响，特别是对 OM 的三种主要细菌病原体的定植。
