Furlan Larissa Lazzarini, Ribeiro José Dirceu, Bertuzzo Carmen Sílvia, Salomão Junior João Batista, Souza Dorotéia Rossi Silva, Marson Fernando Augusto Lima
Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, SP, Brazil.
Universidade Estadual de Campinas (Unicamp), Faculdade de Ciências Médicas, Departamento de Pediatria, Campinas, SP, Brazil.
J Pediatr (Rio J). 2017 Nov-Dec;93(6):639-648. doi: 10.1016/j.jped.2017.03.005. Epub 2017 Jul 15.
Interleukin 8 protein promotes inflammatory responses, even in airways. The presence of interleukin 8 gene variants causes altered inflammatory responses and possibly varied responses to inhaled bronchodilators. Thus, this study analyzed the interleukin 8 variants (rs4073, rs2227306, and rs2227307) and their association with the response to inhaled bronchodilators in cystic fibrosis patients.
Analysis of interleukin 8 gene variants was performed by restriction fragment length polymorphism of polymerase chain reaction. The association between spirometry markers and the response to inhaled bronchodilators was evaluated by Mann-Whitney and Kruskal-Wallis tests. The analysis included all cystic fibrosis patients, and subsequently patients with two mutations in the cystic fibrosis transmembrane conductance regulator gene belonging to classes I to III.
This study included 186 cystic fibrosis patients. There was no association of the rs2227307 variant with the response to inhaled bronchodilators. The rs2227306 variant was associated with FEF in the dominant group and in the group with two identified mutations in the cystic fibrosis transmembrane conductance regulator gene. The rs4073 variant was associated with spirometry markers in four genetic models: co-dominant (FEF and FEF), dominant (FEV, FEF, FEF, and FEF), recessive (FEF and FEF), and over-dominant (FEV/FVC).
This study highlighted the importance of the rs4073 variant of the interleukin 8 gene, regarding response to inhaled bronchodilators, and of the assessment of mutations in the cystic fibrosis transmembrane conductance regulator gene.
白细胞介素8蛋白可促进炎症反应,即使在气道中也是如此。白细胞介素8基因变异体的存在会导致炎症反应改变,并可能使对吸入性支气管扩张剂的反应有所不同。因此,本研究分析了白细胞介素8变异体(rs4073、rs2227306和rs2227307)及其与囊性纤维化患者对吸入性支气管扩张剂反应的关联。
通过聚合酶链反应的限制性片段长度多态性对白细胞介素8基因变异体进行分析。通过曼-惠特尼检验和克鲁斯卡尔-沃利斯检验评估肺量计指标与吸入性支气管扩张剂反应之间的关联。分析纳入了所有囊性纤维化患者,随后是囊性纤维化跨膜传导调节因子基因存在两个属于I至III类突变的患者。
本研究纳入了186例囊性纤维化患者。rs2227307变异体与吸入性支气管扩张剂的反应无关联。rs2227306变异体与优势组以及囊性纤维化跨膜传导调节因子基因存在两个已识别突变的组中的用力呼气流量(FEF)相关。rs4073变异体在四种遗传模型中与肺量计指标相关:共显性(FEF和FEF)、显性(第一秒用力呼气容积[FEV]、FEF、FEF和FEF)、隐性(FEF和FEF)和超显性(FEV/用力肺活量[FVC])。
本研究强调了白细胞介素8基因rs4073变异体在吸入性支气管扩张剂反应方面的重要性,以及对囊性纤维化跨膜传导调节因子基因突变进行评估的重要性。