Patel Janak A, Nair Sangeeta, Revai Krystal, Grady James, Saeed Kokab, Matalon Reuben, Block Stan, Chonmaitree Tasnee
Department of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555-0371, USA.
Pediatrics. 2006 Dec;118(6):2273-9. doi: 10.1542/peds.2006-0764.
Susceptibility to otitis media results from complex interactions among genetic factors of the host, exposure to pathogens, and environmental influences. The objective of this study was to study the role of single-nucleotide polymorphisms of regulatory elements of proinflammatory cytokine genes tumor necrosis factor-alpha(-308), interleukin-1beta(+3953), and interleukin-6(-174), in susceptibility to recurrent otitis media in childhood.
A total of 505 children (296 otitis media susceptible, 209 nonsusceptible as control) were enrolled at 2 sites (Texas and Kentucky). DNA of the children was studied for specific single-nucleotide polymorphisms by restriction fragment length polymorphism assay and confirmed by gene sequencing.
In the overall study group, tumor necrosis factor-alpha(-308) and interleukin-6(-174) heterozygous or homozygous polymorphisms (high cytokine-producing genotypes) were significantly associated with otitis media susceptibility. The same association was found in a match-paired subgroup of 384 subjects. In the overall study group, there was a significant step-wise increase in otitis media susceptibility with increasing number of concomitant polymorphic genotypes. Simultaneous combination of tumor necrosis factor-alpha(-308) and interleukin-6(-174) polymorphisms further increased the risk for otitis media susceptibility. These 2 polymorphic genotypes also were associated with the increased risk for tympanostomy tube placement. Children who had tumor necrosis factor-alpha(-308) polymorphism and were breastfed for <1 month or exposed to cigarette smoke were more likely to be otitis media susceptible.
Our data suggest that tumor necrosis factor-alpha(-308) and interleukin-6(-174) polymorphisms are associated with increased risk for otitis media susceptibility and placement of tympanostomy tubes. Environmental factors such as breastfeeding may modify the risk for otitis media susceptibility in polymorphic individuals.
中耳炎易感性源于宿主遗传因素、病原体暴露及环境影响之间的复杂相互作用。本研究的目的是探讨促炎细胞因子基因肿瘤坏死因子-α（-308）、白细胞介素-1β（+3953）和白细胞介素-6（-174）调控元件的单核苷酸多态性在儿童复发性中耳炎易感性中的作用。
在两个地点（得克萨斯州和肯塔基州）共招募了505名儿童（296名中耳炎易感儿童，209名非易感儿童作为对照）。通过限制性片段长度多态性分析研究儿童DNA的特定单核苷酸多态性，并通过基因测序进行确认。
在整个研究组中，肿瘤坏死因子-α（-308）和白细胞介素-6（-174）杂合或纯合多态性（高细胞因子产生基因型）与中耳炎易感性显著相关。在384名受试者的匹配配对亚组中也发现了相同的关联。在整个研究组中，随着伴随多态性基因型数量的增加，中耳炎易感性呈显著的逐步增加。肿瘤坏死因子-α（-308）和白细胞介素-6（-174）多态性的同时组合进一步增加了中耳炎易感性风险。这两种多态性基因型也与鼓膜置管风险增加有关。具有肿瘤坏死因子-α（-308）多态性且母乳喂养<1个月或接触香烟烟雾的儿童更易患中耳炎。
我们的数据表明，肿瘤坏死因子-α（-308）和白细胞介素-6（-174）多态性与中耳炎易感性增加及鼓膜置管有关。母乳喂养等环境因素可能会改变多态性个体患中耳炎的易感性风险。
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