儿童哮喘治疗转归与血管内皮生长因子A （VEGFA）多态性相关
2012/07/05
摘要
背景：哮喘是一种常见的慢性疾病，表现为气道炎症和气道重构。血管内皮生长因子（VEGF）是一个主要的血管生成调节因子。研究显示，哮喘患者VEGF表达增加，且与气道反应性和气道重构相关。有证据显示，哮喘治疗后能降低VEGF表达，而抑制VEGF后能减少小鼠哮喘症状。因此，血管内皮生长因子A（VEGFA）基因的多态性可能与哮喘的治疗反应相关。
方法：本研究入选131名采用不同手段治疗的哮喘患儿，治疗措施包括激素（丙酸氟替卡松）或白三烯受体抑制剂（LTRA；孟鲁司特）吸入治疗。对肺功能改善（通过检测第1秒用力呼气体积预测值百分数： FEV1预测值%、治疗6个月和12个月后FEV1/FVC、治疗12个月后的哮喘控制）与VEGFA基因2个多态性（rs2146323和rs833058）的关系进行评价。
结果：VEGFA基因多态性rs2146323 A>C与针对ICS治疗的反应相关。AA基因型哮喘患者FEV1预测值%的改善比AC和CC基因型更明显（P= 0.018）。相反，rs2146323的AA基因型与正规LTRA治疗的哮喘患者哮喘未控制相关（P = 0.020)，与周期性LTRA治疗患者FEV1/FVC较差相关（P= 0.044）。此外，多态性rs833058 C>T与周期性LTRA治疗的治疗反应相关。TT基因型患者%FEV1预测值得到改善，但CT基因型和CC基因型患者未见改善（P= 0.029）。
结论：患者对常见哮喘治疗的反应与VEGFA的rs2146323和rs833058多态性相关。如果我们的研究结果能得到证实，将有助于开发出个性化的哮喘治疗方案。
（刘国梁 审校）
Mol Diagn Ther. 2012 Apr 20. doi: 10.2165/11631710-000000000-00000. [Epub ahead of print]
Mol Diagn Ther. 2012 Apr 20. doi: 10.2165/11631710-000000000-00000. [Epub ahead of print]
Source
University Clinic of Pulmonary and Allergic Diseases, Golnik, Slovenia.
Abstract
BACKGROUND: Asthma is a common chronic disease characterized by airway inflammation and structural remodeling. Vascular endothelial growth factor (VEGF), a major regulator of angiogenesis, is elevated in asthma patients. VEGF contributes to airway responsiveness and remodeling. It has been shown that treatment of asthma patients decreases VEGF levels, and inhibition of VEGF diminishes asthma symptoms in mice. Therefore, polymorphisms in the vascular endothelial growth factor A (VEGFA) gene might be associated with asthma treatment response.
METHODS: This study enrolled 131 children with asthma treated with different therapies - specifically, the inhaled corticosteroid (ICS) fluticasone propionate or the leukotriene receptor antagonist (LTRA) montelukast. We performed an association analysis between improvement of lung function - assessed by measurement of the percentage of the predicted forced expiratory volume in 1 second (%predicted FEV(1)), the ratio between the FEV(1) and the forced vital capacity (FEV(1)/FVC) after 6 and 12 months of treatment, and asthma control after 12 months of treatment - and two polymorphisms, rs2146323 and rs833058, in the VEGFA gene.
RESULTS: Polymorphism rs2146323 A>C in VEGFA was associated with response to ICS therapy. Asthma patients with the AA genotype had a greater improvement in the %predicted FEV(1) than those with the AC or CC genotype (p = 0.018). Conversely, the AA genotype in rs2146323 was associated with uncontrolled asthma in patients regularly receiving LTRA therapy (p = 0.020) and a worse FEV(1)/FVC ratio in patients who episodically used LTRA therapy (p = 0.044). Furthermore, polymorphism rs833058 C>T was associated with treatment response to episodically used LTRA therapy. A subgroup of patients with the TT genotype had an improvement in the %predicted FEV(1), compared with no improvement in patients with the CT or CC genotype (p = 0.029).
CONCLUSIONS: Our results showed that treatment response to commonly used asthma therapies (ICS or LTRA) is associated with polymorphisms rs2146323 and rs833058 in VEGFA. With additional replication of this preliminary study, our findings could contribute to the development of individualized asthma therapy.
Mol Diagn Ther. 2012 Apr 20. doi: 10.2165/11631710-000000000-00000. [Epub ahead of print]
上一篇：
蟑螂过敏原诱导远系繁殖小鼠双相哮喘样肺部炎症
下一篇：
环境臭氧和PM2.5水平与哮喘急诊就诊的关系：性别和种族的影响
