METHODS: This was an exploratory study that included 60 participants. Thirty children with non-cystic fibrosis bronchiectasis (NCFB) were compared with 30 age and sex-matched controls. ALOX-15,c.-292 C > T polymorphism was genotyped using TaqMan-based Real-time PCR. LXA4 was measured in BAL using ELISA method.
RESULTS: There was no significant difference between patients and controls regarding ALOX-15,c.-292 C > T polymorphism genotypes and alleles (OR = 1.75; 95% CI (0.53-5.7), P = 0.35) (OR = 1; 95% CI (0.48-2), p = 1). BAL LXA4 level was significantly lower in patients, median (IQR) of 576.9 (147.6-1510) ng/ml compared to controls, median (IQR) of 1675 (536.8-2542) (p = 0.002). Patients with severe bronchiectasis had a significantly lower LXA4 level (p < 0.001). There were significant correlations with exacerbations frequency (r=-0.54, p = 0.002) and FEV1% predicted (r = 0.64, p = 0.001). Heterozygous CT genotype carriers showed higher LXA4 levels compared to other genotypes(p = 0.005).
CONCLUSIONS: Low airway LXA4 in children with NCFB is associated with severe disease phenotype and lung function deterioration. CT genotype of ALOX-15,c.-292 C > T polymorphism might be a protective genetic factor against bronchiectasis development and/or progression due to enhanced LXA4 production.
方法:这是一项包括60名参与者的探索性研究。比较了30名非囊性纤维化支气管扩张症(NCFB)儿童与30名年龄和性别匹配的对照组。ALOX-15,c.使用基于TaqMan的实时PCR对-292C>T多态性进行基因分型。使用ELISA方法测量BAL中的LXA4。
结果:患者和对照组之间在ALOX-15,c方面没有显着差异。-292个C>T多态性基因型和等位基因(OR=1.75;95%CI(0.53-5.7),P=0.35)(OR=1;95%CI(0.48-2),p=1)。患者的BALLXA4水平明显降低,与对照组相比,中位数(IQR)为576.9(147.6-1510)ng/ml,中位数(IQR)为1675(536.8-2542)(p=0.002)。严重支气管扩张患者的LXA4水平明显降低(p<0.001)。与加重频率(r=-0.54,p=0.002)和预测的FEV1%(r=0.64,p=0.001)存在显着相关性。与其他基因型相比,杂合CT基因型携带者显示更高的LXA4水平(p=0.005)。
结论:NCFB患儿低气道LXA4与严重疾病表型和肺功能恶化相关。ALOX-15的CT基因型,c.-292C>T多态性可能是由于LXA4产生增强而导致的支气管扩张发展和/或进展的保护性遗传因素。