Hong Soo-Jong, Kim Hyo-Bin, Kang Mi-Jin, Lee So-Yeon, Kim Ja-Hyung, Kim Bong-Seong, Jang Seong-Ok, Shin Hyung-Doo, Park Choon-Sik
Department of Pediatrics, University of Ulsan College of Medicine, Seoul, Korea.
J Allergy Clin Immunol. 2007 Feb;119(2):398-404. doi: 10.1016/j.jaci.2006.10.031. Epub 2006 Dec 28.
TNF-alpha is a pivotal proinflammatory cytokine increased in asthmatic airways. The TNF-alpha gene family might be linked to asthma or bronchial hyperresponsiveness (BHR), and TNF-alpha production might be modulated by CD14(+) cells.
We investigated the association between asthma susceptibility or asthma-related phenotypes and TNF-alpha (-308G/A) polymorphism and examined the combined effect with CD14 (-159T/C) polymorphism in Korean children.
Asthmatic (n = 788) and control (n = 153) children were evaluated for asthma phenotypes. Genotypes were determined by using the single-base extension method and PCR-restriction fragment length polymorphism.
There was no difference between asthmatic children and control subjects in terms of the allele frequencies of TNF-alpha (-308G/A) and CD14 (-159T/C). Significantly lower PC(20) values were seen in asthmatic (P = .016) children with the TNF-alpha risk allele (-308A). Higher frequencies of 1 or 2 copies of the risk allele were found in asthmatic children with moderate-to-severe BHR to methacholine and exercise compared with control children (adjusted odds ratio of 2.57 [95% CI, 1.30-5.08] and adjusted odds ratio of 2.04 [95% CI 0.99-4.20], respectively). In addition, asthmatic children with risk alleles at both loci had significantly greater BHR than those homozygous for the common alleles (P = .018).
The TNF-alpha promoter polymorphism (-308G/A) might be associated with severe BHR in Korean children with asthma. In addition, these children show a synergistic effect between the TNF-alpha promoter (-308A) and CD14 promoter (-159C) polymorphisms in terms of BHR.
The TNF-alpha polymorphism might be a disease-modifying gene in asthma and modulated by the CD14 gene.
肿瘤坏死因子-α（TNF-α）是哮喘气道中一种关键的促炎细胞因子。TNF-α基因家族可能与哮喘或支气管高反应性（BHR）有关，且TNF-α的产生可能受CD14(+)细胞调节。
我们在韩国儿童中研究哮喘易感性或哮喘相关表型与TNF-α（-308G/A）多态性之间的关联，并检测其与CD14（-159T/C）多态性的联合效应。
对788例哮喘儿童和153例对照儿童进行哮喘表型评估。采用单碱基延伸法和聚合酶链反应-限制性片段长度多态性技术确定基因型。
哮喘儿童与对照儿童在TNF-α（-308G/A）和CD14（-159T/C）的等位基因频率方面无差异。携带TNF-α风险等位基因（-308A）的哮喘儿童的PC(20)值显著更低（P = 0.016）。与对照儿童相比，对乙酰甲胆碱和运动有中度至重度BHR的哮喘儿童中，风险等位基因1或2拷贝的频率更高（调整优势比分别为2.57 [95%可信区间，1.30 - 5.08]和2.04 [95%可信区间0.99 - 4.20]）。此外，两个位点均有风险等位基因的哮喘儿童的BHR显著高于那些常见等位基因纯合的儿童（P = 0.018）。
TNF-α启动子多态性（-308G/A）可能与韩国哮喘儿童的严重BHR有关。此外，这些儿童在BHR方面显示出TNF-α启动子（-308A）和CD14启动子（-159C）多态性之间的协同效应。
TNF-α多态性可能是哮喘中的一个疾病修饰基因，并受CD14基因调节。
