Abderrahman Mami Hospital, Unit Research 12SP15 "Expression Moleculaires des Interactions Cellulaires et de leur mode de Communication dans le Poumon Profond" Ariana; Tunisia, University of Tunis El Manar & A. Mami Hospital Pavillon B. Ariana; Tunisia, 2082, Ariana, Tunisia.
University Tunis El Manar, Tunis Tunisia, Medicine Faculty of Tunis, Djebel Lakdar, Bab Saadoun, Tunis, Tunisia.
Lung. 2017 Dec;195(6):749-757. doi: 10.1007/s00408-017-0058-6. Epub 2017 Oct 9.
To examine the IL-8 expression levels and association of genetic variants with the risk of childhood persistent asthma prognosis.
Overall, 170 asthmatic children and 170 healthy controls were included in this case-control study. The human IL-8 serum levels were measured using ELISA. The IL-8 mRNA expression levels were assessed by a real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods.
The IL-8 expression at both protein and mRNA levels was found to be significantly elevated in asthmatic children compared to healthy subjects (P < 0.0001, P = 0.004; respectively). Higher levels of IL-8 mRNA are detected in subjects with moderate to severe asthma. The presence of IL8-251 A/T (rs4073) and + 781C/T (rs2227306) polymorphisms was significantly associated with an increased risk of asthma (P = 0.002, P = 0.036, respectively). In addition, we noted a significant association between these polymorphisms and an elevated risk of atopic asthma (P < 0.05). For rs2227306 SNP, the highest median level of IgE was detected for the presence of TT genotype (865 ± 99.74 IU/mL). Although, the rs4073 polymorphism conferred a higher risk to develop asthma at an advanced stage of severity (P = 0.008). The rs4073 T and rs2227306 C alleles are considered as risk factors for asthma development. The rs4073 T allele is represented also as a risk factor for asthma severity in Tunisian children.
Both IL-8 gene and protein expression may play a key role in asthma pathogenesis.
检测白细胞介素-8（IL-8）的表达水平及遗传变异与儿童持续性哮喘预后风险的关系。
采用病例对照研究，纳入 170 例哮喘患儿和 170 例健康对照者。采用酶联免疫吸附试验（ELISA）法检测血清中 IL-8 水平，实时荧光定量逆转录聚合酶链反应（qRT-PCR）法检测 IL-8mRNA 表达水平，聚合酶链反应-限制性片段长度多态性（PCR-RFLP）法进行基因分型。
与健康对照组相比，哮喘患儿血清中 IL-8 蛋白和 mRNA 水平均显著升高（P<0.0001，P=0.004）；中重度哮喘患儿 IL-8mRNA 水平更高。IL8-251A/T（rs4073）和+781C/T（rs2227306）多态性与哮喘发病风险增加显著相关（P=0.002，P=0.036）；此外，我们还发现这些多态性与特应性哮喘发病风险升高显著相关（P<0.05）。对于 rs2227306 单核苷酸多态性，TT 基因型患者 IgE 中位数水平最高（865±99.74IU/mL）。虽然 rs4073 多态性在严重程度进展期使哮喘发病风险更高（P=0.008），但 rs4073T 等位基因和 rs2227306C 等位基因被认为是哮喘发病的危险因素。rs4073T 等位基因也是突尼斯儿童哮喘严重程度的危险因素。
IL-8 基因和蛋白表达可能在哮喘发病机制中起关键作用。
