转化生长因子β1基因启动子区C-509T多态性与儿童哮喘易感性及气道重塑关系研究

Association of transforming growth factor-β1 C-509T polymorphism with childhood asthma susceptibility and airway remodeling.

目的探讨转化生长因子β1（TGF-p1）基因启动子区C-509T多态性对儿童哮喘易感性及对气道重塑的影响。方法收集2008年3月至2010年10月新乡医学院第一附属医院呼吸内科和儿科住院及门诊哮喘患儿110例为哮喘组，其中男61例、女49例；选择同期住院非呼吸系统疾病患儿144例为对照组。采用以医院为基础的病例对照研究方法，C-509T多态性用聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP）技术进行基因分型；运用高分辨率CT（HRCT）扫描并测量能显示支气管横截面的气道壁内外径、内外腔面积，通过公式计算出气道壁厚度与外径比（T／D）、气道壁面积占气道总横截面积百分比（WA％）。结果哮喘组C-509T位点T等位基因频率显著高于对照组（P=0．006，OR=1．66，95％CI：1．16-2．37）。相比较TT和TC基因型，CC基因型携带者哮喘患病危险性明显降低（P=0．004，OR=0．46，95％CI：0．27-0．79）。轻中度喘组wA％为（67．41±10．72）％、重度哮喘纽为（73．65±9．94）％，与对照组（63．26±8．12）％比较，差异有统计学意义（P〈0．05）；重度哮喘组T／D值显著高于轻中度组。携带cT和TT基因型患儿的T／D、WA％显著高于cC基因型（P〈0．05）。结论TGF-Bl基因启动子区C-509T位点多态性与儿童哮喘发病相关，同时该位点多态性亦可能是哮喘气道重塑的影响因素之一。

Objective To verify the association of transforming growth factor-β1 C-509T polymorphisms with childhood asthma susceptibility and airway remodeling. Methods A total of 144 controls and 110 asthmatic patients were recruited for this hospital-based case-control study.C-509T site was genotyped using the polymerase chain reaction-restriction fragment length polymorphism method.HRCT were performed in 63 patients with mild asthma, 47 patients with severe asthma and 10 control subjects. Measurement of total airway diameter （D） and lumen diameter （L）was done and then calculate the airway wall thickness （T） and wall thickness to airway diameter ratio （T/D） and the percentage of airway wall area to total airway cross sectional area （WA%）.Results The allele T of C-509T in childhood asthma group was significantly higher than that in control group （P = 0.006, OR = 1.66,95%CI： 1.16-2.37）. There were significant differences for CC genotype distribution between the controls and the asthma patients, and the risk of asthmtl for the childhood with genotype CC was significantly decreased （P = 0.004, OR = 0.46, 95%CI： 0.27-0.79）.Comparison of mild asthma and severe asthma with control subjects revealed significantly higher values of WA% [ （67.41± 10.72）%, （73.65 ± 9.94）% and （63.26 ± 8.12）%, P〈0.05].T/D was significantly different between severe group and mild group （P〈 0.05）. T/D and WA% of asthma patients who carried CT and TT genotype were higher than CC genotype.Conclusion Our results highlight the role of TGF-β1 C-509T T allele as a susceptibility gene for children asthma, and C-509T polymorphism may be one of main factors of airway remodeling.